A border poll on the reunification of Ireland should be held if Britain votes to leave the EU, Martin McGuinness said.
The Sinn Fein leader predicted any exit would be against the democratic wishes of the Irish people.
The DUP is the only large party in Northern Ireland to campaign for Brexit in the June referendum.
Mr McGuinness said: “Such a negative development would represent a political and economic game changer.”
Sinn Fein, the Ulster Unionists and the nationalist SDLP are campaigning to stay in the union.
Mr McGuinness added: “Ireland’s place north and south is in Europe and leading change in Europe.
“If Britain votes to leave the European Union then that could have huge implications for the entire island of Ireland and, given all the predictions, would run counter to the democratic wishes of the Irish people.
“If there is a vote in Britain to leave the EU there is a democratic imperative to provide Irish citizens with the right to vote in a border poll to end partition and retain a role in the EU.”
He said the 1998 Good Friday Agreement which ended decades of the Troubles provided for a border poll to be conducted, with Britain bound to legislate for any change arising.
“I have proposed to (Northern Ireland Secretary) Theresa Villiers that, given the enormous significance of these issues, the British government now give a firm commitment to an immediate border poll in the event Britain votes to leave the European Union.”
An NIO statement said: “The Government set out its position on a border poll in its manifesto at the last election which said: ‘In our view all tests of opinion show that in Northern Ireland today a substantial majority continues to support the Union.
“We therefore feel that the circumstances requiring a border poll are not currently satisfied and that such an exercise would be costly, divisive and a distraction.”