The Foreign Office minister Lord Malloch-Brown has announced he is stepping down as a Government minister at the end of July.
The minister for Africa, Asia and the UN insisted he still "greatly admired" Gordon Brown and that the decision had nothing to do with the "political situation". He added that the decision had been made due to "personal and family reasons".
But the minister's departure, which adds to a long list of recent high profile resignations, is a considerable blow to the Prime Minister. In a statement, Lord Malloch-Brown said: "I have always said that I would not do this job forever. I have strong personal and family reasons for moving on at this time.
"I came into government as a professional, not a politician.
"My decision to step down at the end of July is not in any way a commentary on the political situation. I greatly admire the Prime Minister and continue to support him and his government.
"I joined the Government at his invitation to help promote his international priorities. It has been a great privilege to do that, and to work with him and with David Miliband."
Downing Street said: "The Prime Minister is grateful for the outstanding work that Lord Malloch-Brown has done as Foreign Office minister. The Government has greatly benefited from his exceptional knowledge of Africa, the respect in which he is held by an extensive network of close contacts, and his passion for his work.
"His support in preparing the G20 London Summit ensured that the plans set out enjoyed the widest possible international support."
Lord Malloch-Brown started his career as a journalist before working at the World Bank and then joining the United Nations – rising to become the deputy secretary general.
In June 2007 he was one of the independent so-called "Goats" recruited by Mr Brown to join his "government of all the talents". Another, Lord Digby Jones, resigned after just 18 months as trade minister.
As Africa minister, the peer played a major role in negotiations over how to tackle Robert Mugabe's regime in Zimbabwe. His appointment to the government came as a surprise to many, owing to a series of clashes with the Bush administration when he was at the UN.
He also attracted some controversy, not least owing to his occupation of a grace-and-favour home in Whitehall, previously occupied by John Prescott.
There were also persistent rumours of tensions with his direct boss, Foreign Secretary David Miliband.Reuse content