In 1981 and 1982, two US citizens died from Japanese encephalitis (JE) acquired in China. In 1983, the Centers for Disease Control initiated an evaluation of a purified, inactivated, mouse-brain-derived JE vaccine produced and used in Japan since 1966. Two doses of this vaccine given 1-2 weeks apart evoked neutralizing antibody titers greater than or equal to 8 in only 77% of recipients. After three JE vaccine doses administered 1-2 weeks apart, 99% developed titers greater than or equal to 8. When a third dose was given to 29 participants 6-12 months after the primary series, all developed titers greater than or equal to 16. Reported adverse reactions included injection site tenderness (18%), erythema (6%), or swelling (3%); headache (9%); and dizziness, fatigue, sleepiness, nausea, chills, fever, or lower back pain (less than or equal to 5%). On the basis of this study, three doses of BIKEN JE vaccine are recommended for US citizens who may be at risk of exposure to JE virus.