The former Tennessee senator and ex-Law & Order actor had kept supporters in suspense all summer while he waited to declare his candidacy.
But during an interview on The Tonight Show with Jay Leno on Wednesday night and a Webcast shortly afterwards, Thompson finally made it official.
The 65-year-old is regarded as the most plausible threat so far to Rudy Giuliani, who was the frontrunner for the Republican nomination.
Thompson is now embarking on a five-day tour of crucial early primary states, including Iowa, South Carolina and New Hampshire.
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