A formalin-inactivated Western equine encephalomyelitis (WEE) vaccine prepared in chick embryo cell cultures was evaluated in man. Only occasional mild reactions were noted in 15 volunteers; no meaningful changes occurred in clinical laboratory values during the 12-day observation period. The mean log10 serum neutralizing indicies (LNI's) were comparable for volunteers given either two 0.5-ml doses of vaccine 28 days apart or a 0.5-ml dose followed by a 0.25-ml dose on day 28. Further evaluation in 21 “at-risk” laboratory workers, virgin to WEE virus, supported the data obtained in the volunteer studies; 92% of those given the 0.5-ml to 0.5-ml series achieved LNI's ≥1.7 by 28 days after the second dose, while 88% responded similarly in the 0.5-ml to 0.25-ml group. Vaccine used as a booster in 43 persons with prior WEE experience demonstrated high immunogenicity. At the time of the 0.1-ml intradermal booster dose, 88% of these persons had LNI's of <1.7, whereas by day 28 postvaccination 95% of these had achieved LNI's ≥1.7.