The overall hypersensitivity reaction rate among 14,249 U.S. Marine Corps personnel who received 36,850 doses of an investigational Japanese encephalitis vaccine was 10.3 per 10,000 doses; reaction rates were 16.1 and 10.3 per 10,000 doses for the first two doses, and 2.0 per 10,000 doses for the third. The reaction rate was 26.7 per 10,000 vaccinees. Of 38 reactors, 26 had urticaria and/or angioedema, and 11 had pruritus. Vaccine reaction intervals clustered within 48 hours for dose 1, but the median reaction interval for dose 2 was 96 hours. A history of urticaria or allergic rhinitis was associated with an increased probability of a vaccine reaction.