Northern Ireland Secretary James Brokenshire has resigned for health reasons.
The news was reported by several UK media outlets as Theresa May begins a cabinet reshuffle after losing several ministers in recent months.
Mr Brokenshire is due to have surgery to remove a small lesion in his lung in the coming weeks.
The British Government published letters exchanged by Mrs May and her outgoing minister, confirming the resignation.
Mr Brokenshire observed: "As a result of my forthcoming surgery I will not be able to give the effort, energy and complete focus needed at this important time.
"In the best interests of the people of Northern Ireland and the Government as a whole, with much regret, I believe that the right thing at this time is for me to stand down from my current responsibilities."
The British Prime Minister responded: "You have undertaken some of the most important and demanding jobs in Government [...] with great diligence, determination and good humour.
"I know that you will approach your forthcoming operation in the same way, and I very much look forward to working alongside you again when you are back to full health."
The letters exchanged by James Brokenshire and Theresa May, as the Northern Ireland Secretary hands in his resignation due to ill health pic.twitter.com/Iu104FqE37
— Press Association (@PA) January 8, 2018
Mr Brokenshire was appointed as Northern Secretary when Mrs May became Prime Minister in July 2016, replacing Theresa Villiers.
Alongside two Irish Foreign Affairs ministers, Mr Brokenshire has overseen the ongoing efforts to form a new Northern Ireland Executive.
Negotiations between parties in the North have failed to reach agreement on forming a new Executive since the Assembly election in March 2017.
The Assembly has not sat since last January.
Amid the stalemate, in November Mr Brokenshire moved to bring forward a budget for Stormont from Westminster.
Tánaiste and Foreign Affairs Minister Simon Coveney, who is in Cairo, said he spoke to Mr Brokenshire by telephone this afternoon to wish him well.
File photo of Simon Coveney and James Brokenshire. Photo: Sam Boal/Rollingnews.ie
Minister Coveney said: "His unwavering commitment - in public and in private - over the last year to securing the effective operation of the devolved power-sharing institutions in Belfast has been hugely important.
"While it is not always obvious to the public gaze, very important progress has been made on significant issues over the last year and I believe that a positive outcome can still be achieved. If it is, it will be a testament to the quiet, understated but hugely valuable work of James Brokenshire."
He added: "In the six months since my appointment as Minister for Foreign Affairs and Trade, I have worked closely with James and I have come to value and appreciate his professionalism and his friendship."
In a statement, DUP leader Arlene Foster sent her best wishes to Mr Brokenshire and his family.
She said: "Since becoming Secretary of State in 2016, Mr Brokenshire had immersed himself fully in the role by dedicating long hours to trying to make progress.
"James leaves the role with a very intimate knowledge of Northern Ireland and I look forward to working with him again in the future.”