The Isle of Man is about to start a "journey into the unknown" after the UK voted to leave the European Union, Chief Minister Allan Bell said.
People in the Crown dependencies of the Isle of Man, Jersey and Guernsey could not vote as none of them are in the EU.
But those in Gibraltar, a British overseas territory, were given a vote and overwhelmingly voted to remain.
Mr Bell said the referendum marked the "start of a journey into the unknown for both the UK and the Isle of Man".
"This situation is without precedent," he added, noting that the UK's withdrawal "will have a significant impact" on the island.
The result means the Isle of Man will now have to seek a replacement for its Protocol 3 relationship with the EU, which allows free trade in manufactured goods and agricultural products.
Mr Bell said the Isle of Man was "well-prepared" but acknowledged the "need to work closely with UK politicians to ensure we understand the UK's direction of travel, and that they understand the implications for us.
"It will be vital that our interests are not overlooked."
Earlier this year Lord of the Rings star and Isle of Man resident John Rhys-Davies launched a petition demanding the right to vote in the EU referendum for those living in British Crown dependencies.
The 71-year-old said the referendum was "one of the most important [and] constitutionally significant events in recent times".