Transport Secretary Ruth Kelly is to step down from the government at the next cabinet reshuffle.
The mother-of-four told the Labour conference it was time to "step back" from politics and put her family first.
There had been reports she was unhappy with Gordon Brown's leadership, but she described him as a "towering figure".
Mr Brown told the BBC Ms Kelly had informed him of her plans in May, adding: "There are no political issues between Ruth and me."
Mr Brown, who sought to reassert his leadership in his conference speech on Tuesday, denied suggestions more resignations might follow.
She also used to be education secretary. This comes as Labour is trying to break out of the downfall they've been having as of the last two years. :eek: