Police said the Bolton man was riding a BMW motorbike when it collided with a Citroen car driven by a local man on Hailwood's Rise on the (A18) Mountain Road at 06:45 BST.
The rider was treated at the scene but was pronounced dead on arrival at Noble's Hospital.
Both vehicles were travelling in the direction of Douglas.
Insp Dave Dobbie said it was a "very sad outcome".
Police closed the road for four hours following the crash and are appealing for witnesses.

The Israeli ambassador to the UN called the database a "blacklist" and said the body was acting obsessively against it.
But the Palestinian envoy said the move was a "message of hope" for his people.
Settlements built on territories occupied by Israel in 1967 are considered illegal under international law, but Israel disputes this position.
About 500,000 Jews live alongside 2.5 million Palestinians in the West Bank and East Jerusalem.
Thirty-two of the 47 members of the Geneva-based Human Rights Council voted on Thursday to adopt the motion calling for the establishment of the database.
None voted against the motion, while 15, mostly European nations, abstained.
The BBC's Yolande Knell in Jerusalem says the database will provide a resource for any organisation wanting to divest from companies involved in Israel's occupation of Palestinian lands.
It will potentially include a number of Israeli and international firms working in industries from banking to construction and security services, our correspondent adds.
The Palestinians have been campaigning for tougher sanctions against settlements.
The Palestinian envoy to the UN said that the passage of this resolution and others by the Human Rights Council were a "message of hope" to his people.
"Israel continues to systematically violate the inalienable rights of the Palestinians while enjoying impunity from the international community," Ibrahim Khreisheh added.
Israeli Prime Minister Benjamin Netanyahu called the body "an anti-Israel circus which attacks the only democracy in the Middle East and ignores the blatant violations of Iran, Syria and North Korea".
He added that it was absurd to condemn Israel rather than deal with attacks by Palestinians on Israelis and by so-called Islamic State in Europe.

The offence occurred in the first-round, second-leg match against Rwanda, which Uganda won 2-1 to secure a 3-2 aggregate victory.
However, Uganda's Aheebwa James had different dates of birth on his passport and his inter-clubs licence.
Rwanda have been reinstated and will take on Egypt in the second round.
The Rwandan Football Federation had challenged the eligibility of Tumwesigye Frank, Aheebwa James, Lwalirwa Halid and Kizza Martin.
Only James was found to have different birth dates: 19/5/1998 on the passport, and 27/3/1997 on his Confederation of African Football Inter-clubs licence.
Although both dates place James within the age limit for the competition, the rules state that both dates must match.
A 55-year-old motorcyclist from Greater Manchester has been killed in a crash involving a car on the Isle of Man.
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Israel has criticised the UN Human Rights Council for voting to establish a database of firms doing business in settlements in the occupied West Bank.
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Uganda have been disqualified from qualifying for the 2017 Under-20 Africa Cup of Nations for fielding an ineligible player.