The resignation of Work and Pensions Secretary Andrew Smith has come at a difficult time for his department, fellow politicians say.
Mr Smith's departure comes ahead of a Cabinet reshuffle
Mr Smith quit on Monday, saying he wanted to spend more time with his family and constituency.
Labour's former chief whip, Nick Brown, said the government would be "weakened" by his departure.
Conservative shadow pensions secretary David Willetts said Mr Smith had suffered a "miserable" few months.
Mr Smith, 53, has been in the work and pensions job since 2002 and is seen as an ally of Chancellor Gordon Brown.
Friends of Mr Smith have suggested his mind had been made up by arguments with government advisors about the extent of possible cuts to disability payments.
The interim findings of a government-commissioned review of pensions are due in coming weeks, addressing the question of whether people should be forced to save.
Nick Brown said the upcoming reform of the department made it a difficult time for change at the top.
He described Mr Smith as "the master of the detail".
"He has presided over a very, very complex series of negotiations and it is not a good time for him to go, which is why I say the government will be significantly weakened by his departure."
He added that negative press briefings could have contributed to Mr Smith's resignation.
"Andrew has been consistently briefed against in the newspapers all through the summer and I am certain that he will have taken this to heart, although that doesn't mean that I wouldn't take his letter at face value," he told Channel 4 News.
"He is a good man, and the government is weakened by his departure."
Conservative shadow pensions secretary David Willetts said he could understand why Mr Smith has decided to go.
"He has had a wretched few weeks and months with Downing Street briefing against him," he told BBC News 24.
But he argued his plight had been nothing compared to the insecurity felt by many pensioners.
"He just didn't ever get to grips with the scale of the pensions crisis that we face," added Mr Willetts.
Liberal Democrat work and pensions spokesman Steve Webb said the new secretary of state would have to reverse the drive towards means testing and restore confidence in company pensions.
'Big questions remain'
period in office will be remembered as one when the crises in company pensions
grew unchecked, where mass means-testing was the order of the day and the
pensions system became more complicated than ever," he said.
With Mr Smith saying he wanted to spend more time on issues in his Oxford East constituency, Steve Goddard, Lib Dem prospective candidate for the seat, accused him of worrying about his election prospects.
"He's realised his constituency is in danger of slipping away from him because we are running him pretty close," Mr Goddard told BBC News Online.
Mary Francis, director-general of the Association of British Insurers, said Mr Smith's departure had come at a crucial time.
"Concern about whether as a nation we are saving enough for retirement has been growing during Andrew's time as secretary of state," she told BBC News Online.
"He has tackled some useful specific issues but big strategic questions remain for his successor to deal with."