Mostow, S. R., S. C. Schoenbaum, W. R. Dowdle, M. T. Coleman, H. S. Kaye and J. C. Hierholzer (Respiratory Virology Unit, NCDC, Atlanta, Ga. 30333). Studies on inactivated influenza vaccines. II. Effect of increasing dosage on antibody response and adverse reactions in man. Amer. J. Epid., 1970, 92: 248–256.—Purified A2/Japan/305/57 influenza vaccine prepared by zonal ultracentrifugation was given subcutaneously in graded doses of 300 CCA units to 4800 CCA units to groups of prisoner volunteers. Reactions to even the highest levels of vaccine were minimal, with less than 1% of the volunteers developing fever. Serum antibody response measured by hemagglutination-inhibition of the homologous virus progressively increased with increasing vaccine dose. The 300 CCA unit vaccine produced a 7-fold increase in mean homologous antibody, whereas the 4800 CCA unit vaccine produced a 35-fold increase. Higher levels of vaccine also stimulated antibodies that were more broadly reactive with the recent 1967 A2 influenza strains. The presence of neutralizing activity against A2/Japan/305/57 virus in post-vaccination nasal washings also correlated closely with vaccine dosage and serum HI antibody titers. Results presented here with human subjects support our earlier findings in mice that increased antigen concentrations produce broader antibody response to heterologous strains and probably greater protection against disease.