The North's pro-agreement parties have expressed regret at the Northern Secretary's resignation but said the peace process must not suffer as a consequence.
The Ulster Unionist deputy leader, Mr John Taylor, described Mr Peter Mandelson's departure as "most untimely and damaging", adding that the Northern Secretary had paid a "very high price" for his actions.
"We in Ulster know how hard Peter Mandelson worked to implement all aspects of the Belfast Agreement. Unionists did not agree with all his decisions but I personally want to place on record my appreciation of his efforts to bring lasting peace and political stability to Northern Ireland," Mr Taylor added.
The North's Deputy First Minister, Mr Seamus Mallon, said there had been "significant advances" in the peace process during Mr Mandelson's time in office.
"Although the Secretary of State and I have differed on a number of issues of policy, he has undoubtedly brought energy and commitment to carrying forward the policy of the British government. His resignation comes at a time of difficulty for the process. I hope that the two governments and all the parties will redouble their efforts to overcome these difficulties to secure the full implementation of all aspects of the Good Friday agreement," Mr Mallon said.
The Sinn Fein president, Mr Gerry Adams, said although his party had been in disagreement with Mr Mandelson over many issues, he "wished him well for the future". He hoped the British government would not now be distracted by the fallout from the resignation.
"This is a defining period in the search for a sustainable process towards a democratic peace settlement on this island. And it requires a strategic approach by London, and particularly a very focused commitment by the British Prime Minister himself," he added.
Paying tribute to Mr Mandelson, the Alliance Party leader, Mr Sean Neeson, said the former Northern Secretary had approached the peace process "fairly and with an even hand".
"It is very unfortunate that the Secretary of State has had to step aside at this very sensitive and critical stage of the political process. The current circumstances are difficult, and for a major change to occur will not make things easier," he said.
The Northern Ireland Women's Coalition said it was "sorry" to see Mr Mandelson go "so abruptly". The task of implementing the Belfast Agreement, however, had to be "larger than one person's political fortunes", a party MLA, Prof Monica McWilliams, said.