Liam Fox's resignation forces David Cameron into a Cabinet reshuffle he does not want.
The Prime Minister has made clear that he wants stability in the senior offices of state, and until the Werritty scandal reared its head there was no question of Fox, fresh from a successful campaign in Libya, facing the boot.
Mr Cameron will not relish seeing his former leadership rival, who is a darling of the Tory right, on the backbenches where he can become a focus of discontent with the coalition Government.
It is not thought likely that the PM will use his Defence Secretary's departure as an excuse for a wholesale shake-up of his Cabinet team.
Northern Ireland Secretary Owen Paterson and International Development Secretary Andrew Mitchell are being tipped as possible contenders for the defence job.
Both are seen to have performed well in low-profile Cabinet posts and could be moved without setting off a "domino effect" of changes throughout the top team.
Other options being discussed in the corridors of Westminster include promotion for Transport Secretary Philip Hammond or even a return to the frontbenches for Major-era defence and foreign secretary Sir Malcolm Rifkind.
Mr Cameron believes ministers need to be given enough time in a post to impose themselves on their departments and see their policy programmes through. In his eyes, many of the failings of Tony Blair's administration can be traced back to his predecessor's fondness for regular - and often botched - reshuffles.
Apart from the forced resignation of David Laws due to an expenses scandal after just 17 days as Chief Secretary to the Treasury, Mr Cameron has completed 17 months in office with his initial top team still in place.
Although he was annoyed by a series of leaks of documents from the Ministry of Defence - all of which were suspiciously helpful to the military's case for a generous funding settlement - the PM has given no indication that Dr Fox's position might be at risk.
To an extent, Cabinet stability was imposed on Cameron by last year's coalition deal, which allotted ministerial posts to Conservatives and Liberal Democrats according to a formula which can only be amended through awkward negotiations with Deputy Prime Minister Nick Clegg.
Dr Fox's departure will be greeted with fury by many on the Tory backbenches, who have made clear they were looking to Mr Cameron to protect him against allegations which some see as largely irrelevant to his ability to do his job.
The Defence Secretary was given strong backing in the Commons on October 10 from a string of Tory MPs, including influential grandees like Sir Malcolm Rifkind, Defence Committee chairman James Arbuthnot and former leadership contender David Davis.
His stock has risen among traditionalist Tories since he achieved a creditable third place in the 2005 leadership contest, and it is likely that he will be seen as a standard-bearer for the right on the backbenches.
He has left little doubt of his distaste for coalition with Liberal Democrats and has been seen as one of the "neo-con" hawks within Cabinet on issues like the renewal of Trident, relations with Israel and sanctions on Iran.
Mr Cameron will be concerned that in losing his Defence Secretary, he may have created a powerful backbench voice challenging the compromises of coalition and demanding a more authentically Conservative policy agenda.