In a double blow, Africa minister Mark Simmonds announced his immediate departure from the Foreign Office and that he would stand down as the MP for Boston and Skegness at next year's general election.
The Lincolnshire constituency is seen as one of Ukip's best chances of gaining its first ever MP.
At its centre is Boston, often cited as an example of a town that has struggled to cope with a sudden increase in immigration in recent years.
Mr Simmonds hinted about the pressure from the Eurosceptic Ukip in his resignation statement to his local party, saying a Conservative win next year would deliver, among other things, the "all-important in/out EU referendum" in 2017.
However, he also blamed his decision to stand down on the lack of support for MPs whose families live far from London.
"Despite the enjoyment and personal fulfilment I have found in this role, the lack of support available to MPs with families outside of London and the sacrifice to my family life, has become intolerable," he said.
He became the second Foreign Office minister to announce his resignation in less than a week.
Last Tuesday Baroness Warsi quit in protest at the government's stance on Gaza. No 10 insisted the two resignations were not linked.