Irish Justice Minister Dermot Ahern has said substantial referendum returns show that Ireland has rejected the European Union reform treaty.
Electoral officials expect to confirm the result later.
Mr Ahern based his conclusion on tallies of votes produced nationally by election observers as well as early official returns.
They showed the "no" camp ahead in the vast majority of Ireland's 43 electoral constituencies, while pro-treaty voters were clearly ahead in only a few.
The expected result will send shock waves throughout the EU.
Ireland was the only member to subject the Lisbon Treaty to a popular vote, while other countries have been ratifying the painstakingly negotiated pact only through their national governments.
Mr Ahern said "We're in uncharted waters."