Custom controls could have to be set up at the Irish Republic's border with Northern Ireland in the event of a Brexit vote, the Taoiseach has warned.
Enda Kenny made a plea to Irish people living in Britain to vote remain next month, saying Ireland would be one of the worst affected countries should the UK choose to leave the European Union.
The Irish leader, speaking in London, said Irish people make up a "substantial" part of the electorate and urged them to use their vote.
Irish citizens living in the UK will have a vote on June 23, alongside British citizens who are living in Ireland.
Campaign Group Irish 4 Europe estimates there are around half a million first generation Irish living in England, Scotland and Wales, and say the number rises to the millions when second and third generation are considered.
Kenny spoke as he prepared to watch his home county of Mayo take on London in a Gaelic Football Championship match in Ruislip.
A firm supporter of the Remain campaign, Kenny said: "We would say, with particular reference to the Irish people living in Britain, this is a really important decision. Its outcome would affect people in Northern Ireland, it would affect Ireland itself and obviously will have an impact upon the European Union for many years to come."
Asked what might happen in the event of a vote for Britain to leave the EU he said there would have to be "significant, complex and difficult negotiations".
He added: "Ireland in Europe would still stand by Britain being a member of the Union and of its importance but I have no idea what other European countries, how they would look at Britain whether they decide to leave, given the fact that we've come a long way since the 1970s.
"So whether there would be border controls or custom controls, these things are a possibility but obviously they would require some very serious negotiations and my preference for the Irish electorate who have a significant part in this referendum is to vote to stay, for Britain to stay as a strong and central member of the European Union for the future."
Kenny said Ireland and Northern Ireland would be "most adversely affected" in the event of a Brexit vote.
Earlier this month, following his election to lead a minority government in Ireland, Kenny spoke with the Prime Minister telling him of his plans to do what he can to help "reach out to Irish citizens" in the referendum campaign.
The Irish leader is set to make a series of visits to Britain and Northern Ireland in the run-up to the vote.
Crowds of supporters, decked out in the green and red of Mayo, were handed leaflets as they entered the GAA ground urging them to vote remain.
One matchgoer - 26-year-old Barbara McKenna, who works as a nurse in London but is originally from the border county of Monaghan - said the idea of border controls would be "awful".