A unique opportunity occurred in February 1977 to assess the efficacy of an influenza virus vaccine given to military personnel in doses of 400 chick cell-agglutinating (CCA) units of A/Victoria/3/75, 400 CCA units of A/New Jersey/76, and 500 CCA units of B/Hong Kong/72 viruses. After cessation of all influenza virus vaccine administration in mid-December 1976, approximately 200 unvaccinated U.S. Air Force personnel arrived per week beginning February 1, 1977, at Lowry Air Force Base, Denver, Colorado. Arriving unvaccinated personnel were assigned to one of 12 units with previously vaccinated personnel. A sharp outbreak of influenza A occurred on the base during February that was due to an A/Texas/1/77-like virus, a variant of the A/Victoria/3/75 prototpye. Fifty-four cases of influenza A were documented in the student population on the base. During the two-week peak of the outbreak, attack rates were 10-fold higher in unvaccinated than in vaccinated students, and the overall estimate of vaccine efficacy was 80%. Thus, despite animal tests suggesting considerable antigenic drift, a vaccine containing influenza A/Victoria/3/75 virus provided good protection against the variant strain.