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In 1979, Keyes recieved a PhD in government from Harvard University. He joined the U.S. Department of State in 1978, as a protege of U.N. ambassador Jeane Kirkpatrick in the Ronald Reagan administration, staying put there until 1987 after disagreement on U.N. funding. He was a U.S. Ambassador to the United Nations Economic and Social Council. Keyes has, however, said he was critical of the United Nations.
After resigning, Keyes ran for the U.S. Senate in 1988, losing to a Democrat incumbent, representing Maryland. He ran again for the Senate in 1992, once again losing to Democratic Senator Barbara Mikulski.
In spite of his loss, Keyes became the host of a radio talk-show, America's Wake-Up Call: The Alan Keyes Show, which was nationally syndicated. The show strongly championed conservative causes.
In 1996, Keyes ran for President of the United States, but he lost in the race to Bob Dole. Keyes ran again in 2000, staying in the race until he lost to George W. Bush.