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At a San Francisco Air Force base, the crew of a B-17 Flying Fortress, nicknamed the "Mary Ann," prepares for a routine flight to Hawaii.  The crew, consisting of Captain Irish Quincannon, co-pilot Bill Williams, bombardier Tommy McMartin, navigator Monk Hauser, Crew Chief Robbie White, assistant Crew Chief Corporal Weinberg and radio operator Peterson, are joined by two new soldiers, assistant radio operator Chester and aerial gunner Joe Winocki.

This is Chester's first flight and he is enthusiastic about it.  Winocki, on the other hand, had wanted to be a pilot, but failed flight school and now, bitter about his disappointment, is counting the days until his enlistment is over.  As the Mary Ann flies over the Pacific on 7 December 1941, the crew hears Japanese voices over their radio and soon learns that Hickam Air Field in Pearl Harbor is under attack.  The news turns Winocki's cynicism around, and he announces that he is now in the air force for the duration of the war.

The flight is diverted to an emergency air field on Maui, where the crew finishes emergency repairs just before fifth columnist snipers advance toward the plane.  Despite the danger, the Mary Ann heads for Hickam.  When the crew lands, they learn that McMartin's sister was wounded during the bombing.  They have time to visit her briefly in the hospital before they are sent out, fully armed, to Manila, which has also been devastated by Japanese bombers.  Flying along with the crew is pursuit pilot Tex Rader.

Before a fuel stop on Wake Island, they receive a shortwave communication reporting that McMartin's sister will recover.  The Marines on Wake, knowing that they are facing almost certain annihilation, hand the Mary Ann's crew letters to mail to their families and also persuade them to take their little dog Tripoli along with them when they leave for Manila.  White is eager to reach Manila because his son is a pilot with the air force there.  Upon landing at Clark Air Force Base, however, he receives the sad news that his son was killed during the first Japanese strike.  The Mary Ann is loaded with bombs and when the Japanese return, the crew engages in a fierce battle during which Quincannon is fatally wounded, and Chester is also killed.

Back on the ground, the crew hurriedly salvages parts from other planes to rebuild the badly damaged Mary Ann.  When Manila falls to the Japanese, the Mary Ann heads for Australia with Rader as their new co-pilot and a former Marine as assistant radio operator.  On the way they spot a Japanese fleet and radio their position to the Allied fleet.  During the ensuing battle, the Japanese are routed.  Later, the men prepare to lead an attack on Tokyo.