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When Lt. Col. James H. Doolittle calls for volunteers for a top-secret Army Air Force mission, pilot Lieut. Ted Lawson is one of many men to offer his services. Lawson and his B-25 crew, co-pilot Dean Davenport, gunner David Thatcher, bombardier Bob Clever and navigator Charles McClure, are sent for training at Eglin Field in Florida, and speculate along with the other crews about the nature of the mission. During the first of many briefings, Doolittle informs the men that the mission will be tough and dangerous and encourages anyone with doubts to drop out. Ted's friend and fellow pilot Bob Gray suggests to Ted that because he has recently married, he has too much to lose, but Ted shrugs off Bob's concerns. Even after he finds out that his wife Ellen, who shows up unexpectedly at the training camp, is going to have a baby, Ted remains determined to continue the mission. A devoted, sympathetic wife, Ellen supports Ted's decision and assures him that she is unafraid of the future. While still keeping the details of the mission secret, Doolittle and naval lieutenant Miller then begin training the crews for short-distance take-offs. As with all the B-25 crews, Ted and his men, who have named their plane "The Ruptured Duck," initially have trouble performing the difficult maneuver, but eventually master it. Then, after ten weeks of training, the men are called to a briefing in the middle of the night and are told that they are leaving immediately for the Alameda Naval Air Base near San Francisco. Ted says a hurried, brave goodbye to Ellen, who promises to write him a letter every day, even though she knows he will never receive them.
In San Francisco, as the planes are being loaded onto the U.S.S. Hornet , a Navy aircraft carrier, Ted learns that another crew has been dismissed from the mission because their plane developed minor mechanical problems. Although "The Ruptured Duck" has been having its own minor problems, Ted decides not to say anything about them, for fear that the plane will be grounded. Soon after the huge ship sets sail, Doolittle finally reveals to the men that they will be conducting the first ever bombing mission on Japan. When Ted and the others are told that the planes are to take off from the deck of the carrier, a feat never before attempted, they fully understand the purpose of their training. That night, Ted and Bob discuss the mission and agree that, while they do not hate the Japanese people, they have no qualms about the bombing raid. As the Hornet approaches the Japanese coast, Doolittle gives the men a final briefing, noting that while all of the targets are military, some Japanese civilians will be killed. Once again, Doolittle offers the men a chance to back out, but no one accepts. The next day, the carrier is spotted by the Japanese, forcing the mission, which had been planned for night, to start early. Doolittle, who has ordered the ship's crew to push overboard any plane that fails to start quickly, is the first to take off. "The Ruptured Duck" has trouble starting, but a determined Ted gets the engine going just in time. Although its left engine is misfiring, "The Ruptured Duck" drops its bombs over Tokyo and heads for the free Chinese coast, where crude airstrips have been built. As they are flying there, however, a storm blows in, causing Ted to crash-land just short of the beach. The plane sinks, but the crew swims to shore. All but David are injured, and Ted's leg is severely cut.
Soon after, sympathetic Chinese villagers appear and carry the Americans to safety. Ted and the others are befriended by a Chinese resistance fighter nicknamed "Guerilla Charlie," who helps them to a small town. There Dr. Chung attends to the men's wounds, but as he has no medicine, orders that they be carried to his father's hospital sixteen miles away. With the Japanese Army not far behind, the men reach the hospital and learn that another crew has been rescued and is on its way there. Although the two crews enjoy their reunion, Ted is told that his leg, which has developed gangrene, must be amputated. While recalling happier days with Ellen, the near-delirious Ted faces the operation with courage. Later, having recovered enough to be moved, Ted is evacuated to Chungking along with the other injured men. After thanking their Chinese rescuers, who helped save many other Americans, including Bob, the crew of "The Ruptured Duck" returns to the U.S. Ellen then receives a phone call from Doolittle and learns about Ted's injury and his refusal to see her until he has received his artificial leg. Urged by Doolittle and her mother, the now visibly pregnant Ellen goes to see Ted at the hospital and, after reassuring him that she is still very much in love, embraces him.