This report summarizes the clinical trials of the A/USSR/77 (H1N1) influenza vaccines performed in 1978. A total of 2,091 subjects participated in these trials. The results of these clinical trials indicated that two doses of H1N1 viral antigen were necessary to produce serum titers of hemagglutinin-inhibiting (HAI) antibody of >1:40 in 80% or more of the test subjects younger than 25 years of age, who were unlikely to have experienced natural infection during the earlier period of prevalence of H1N1 virus (1947–1957). Only one dose of the A/Texas/77 (H3N2) or B/Hong Kong/72 antigen was necessary to stimulate equivalent titers of HAI antibody in serum. Thus, previous natural exposure to H1N1 viruses primed individuals 26 years of age or older to respond to H1N1 antigens. No major differences in antigenicity were noted between whole-virus and split-virus vaccines. No differences in reaction indexes measuring systemic reactions were noted when vaccine types were compared. Only one vaccine was associated with a reaction index appreciably higher than that of placebo. The relatively uniform antibody responses observed were attributed to the newer methods of vaccine standardization introduced after the clincal trials in 1976. No cases of vaccine-related neurological problems, including Guillain-Barré syndrome, were found during these trials. Vaccines containing 7–21 µg of each viral antigen were antigenic and were well tolerated.