Recently defined aspects of cellular and humoral antiviral immunity were evaluated in 10 young adults given influenza vaccines containing A/USSR/77 (H1N1) antigens. Cytotoxic lymphocytes were measured by using cryopreserved lymphocytes as effector cells and syngeneic, virus-infected lymphocytes as target cells. An assay previously developed in this laboratory was adapted for the measurement of antibody-dependent, complement-mediated cytotoxicity. Antiviral cytotoxic lymphocyte responses were detected in 5 of 10 volunteers between 3 and 10 days after the initial vaccination. These responses were found both in individuals who were previously primed and in individuals who were not primed to influenza A/USSR/77 antigens. The complement-mediated lysis assay was found to be more sensitive than the hemagglutination inhibition test and probably detected antibodies to both subtype-specific and cross-reactive antigenic determinants. These responses to influenza antigens are similar to those obtained in studies of murine influenza which indicate that cytotoxic lymphocytes and antibody-dependent, complement-mediated cytotoxicity have a role in the early response to acute infection.