Coming in rapid succession over the past two weeks, the departures included Susan Wagner, a founding partner and vice chairman, who will retire at the end of June, and Robert Capaldi, who has already left and was senior client strategist for Chief Executive Laurence Fink.

New York-based BlackRock also announced the departures of two of the firm's most prominent portfolio managers, chief equity strategist Bob Doll and energy sector fund star Daniel Rice. Rice will help transition some of his funds, a process that is expected to last through December and Doll will retire at the end of month, BlackRock said.

Wagner's departure was the most significant of the four as it further signals the end of growth through large acquisitions for BlackRock, according to two people with knowledge of the situation.

One of the original partners of the firm, Wagner joined from the Lehman Brothers mortgage department when Fink opened for business in 1988. Frequently named to published lists as one of the most powerful women in business, Wagner will join BlackRock's board of directors where she will continue to have a say on strategy, spokeswoman Bobbie Collins said.

Some BlackRock employees are worried Wagner's departure may signal bigger changes or further departures from the firm, possibly including Fink moving into a government role, according to two people familiar with the situation. One of these people, and another person familiar with the situation, said further senior-level changes are expected in the coming weeks.

"People are speculating that Sue is stepping down because Larry is going to make a move for government," said the person, who declined to be identified because he was told this in confidence. For the past several months, rumors have been circulating that Fink is a candidate for U.S. Treasury Secretary if President Barack Obama is re-elected in November.

There's also concern about how BlackRock is handling the other departures. For example, client relationship managers at BlackRock, whose job it is to assuage investors' concerns, did not have any talking points to discuss regarding the Rice situation after it became known that he would be leaving, according to one person who spoke to a client relationship manager at the firm, and declined to be identified because the conversation was confidential.

"People are getting client calls and they have no talking points," the person said.

BlackRock has maintained that most of the changes were part of the firm's necessary restructuring after digesting two huge mergers in the past six years and growing to a previously unprecedented size of $4 trillion.

Three years ago, BlackRock absorbed Barclays Global Investors and its $1.8 trillion of assets, doubling the firm overnight. That followed the 2006 acquisition of almost $600 billion in Merrill Lynch's fund division.

CEO Fink has lately been saying that he is done with mega-mergers for the foreseeable future. Formerly BlackRock's head of corporate strategy, Wagner coordinated acquisition activity including the Barclays deal and the Merrill buy.

BlackRock spokeswoman Collins said the recent departures among fund managers and senior staff were not related. "The personnel changes people are seeing are neither related nor a trend," she said.

Investors have so far brushed off the departures. Shares of BlackRock rose 5.3 percent over the past month, outpacing the S&P 500's 1.5 percent gain.

As Wagner departs, BlackRock has made several recent high-level hires with a non-U.S. focus. Former Swiss central bank chairman Philipp Hildebrand, who quit that post after a controversy involving his wife's currency trading, joined as vice chairman. And Mark McCombe, who was Chief Executive Officer in Hong Kong for HSBC, came on board as BlackRock's Chairman for Asia-Pacific.

Capaldi's advisory role was eliminated when he left, BlackRock said, but his prior role heading the firm's U.S. and Canadian institutional business was filled in 2011 by the hire of Edwin Conway, a senior managing director from private equity shop Blackstone.

The end of mega-mergers is likely good news for BlackRock clients. Industry experts wonder if some of BlackRock's recent issues, particularly the questions regarding energy fund manager Rice, stem from failures in oversight due to the big mergers in recent years.

Rice left in the wake of a potential conflict of interest that involved his family business. The energy mutual funds Rice had co-managed at BlackRock increased their holdings in Alpha Natural Resources (ANR.N) after that company formed a joint venture with a unit of a natural gas drilling company founded by Rice.

"It is hard to explain how if they knew about (the Rice situation), they were okay with it," said Russ Kinnel, director of mutual fund research at Morningstar. "The mergers may have left some gaps in their compliance."

Doll, who joined BlackRock in 2006 when it acquired Merrill Lynch's money management unit, will retire at the end of June. In January, BlackRock removed language from the prospectus of Doll's funds stating that they used "proprietary" quantitative investment models, instead saying the models came from "third-party research firms.

And two of Doll's three funds, BlackRock's Large Cap Core Fund (MCLRX.O) and Large Cap Value Fund (MALVX.O), have trailed the performance of the vast majority of similar funds over the past three years.

BlackRock CEO Fink has a history of moving on quickly when fund managers disappoint.

"We're very confident in Larry Fink," said Macrae Sykes, an analyst at Gabelli & Co in Rye, New York. "He will swiftly and appropriately address any issues with underperformance or reputational risk."

"Compliance and reputational care are very, very important to BlackRock," BlackRock spokeswoman Collins said.

The recent string of departures may concern financial advisers who work with BlackRock, Kinnel said. BlackRock has said it wants to double its retail mutual fund business to $600 billion by the end of 2014, largely by targeting registered investment advisers.

"It's not yet to the point where this will send advisers fleeing, but it doesn't give you a particularly good feeling," Kinnel said.

(Reporting By Aaron Pressman in Boston and Jessica Toonkel in New York; Editing by Jennifer Merritt, Alwyn Scott, Edward Tobin and Bernard Orr)

• A Permanent Economic Emergency