A proliferative assay employing virus-infected, fixed monolayers was used to examine the response of PBL and lymphocyte subpopulations to measles, mumps, and vaccinia viruses. The response obtained in this assay was shown to be virus specific. In individuals previously exposed to mumps or vaccinia viruses, a substantial proliferative response was elicited. In contrast, only a small number of individuals responded to measles virus even though they were seropositive for this virus. In the responders, the proliferation to each of the viruses was essentially limited to the T cell fraction and more specifically to the IgG Fc receptor-bearing T cell, the T gamma cell. The response was not dependent on the presence of antiviral antibody in the assay and was therefore apparently not related to the ADCC activity of the T gamma population. The failure of the T non-gamma cell to proliferate was not due to HLA restriction since a response in this cell population could not be elicited on infected autologous skin fibroblasts. The functional significance of the T gamma cell response is not established although a possible immunoregulatory role is considered.