Recurrent infections with respiratory syncytial virus (RSV) have been well documented despite serological evidence of prior exposure of the host and the absence of clear evidence of antigenic variation of the virus. Therefore, human mononuclear leukocytes, as well as purified lymphocytes and monocytes-macrophages, were exposed to RSV in vitro and examined for expression of viral antigens by using indirect immunofluorescence with monoclonal antibodies to RSV. RSV infected both human monocytes-macrophages and lymphocytes in vitro. RSV infection resulted in both a decrease in the number of T helper phenotype cells and an increase in T suppressor phenotype cells. RSV proteins were disproportionately expressed by atypical or lymphoblastoid cells, many of which were of the T suppressor phenotype. Circulating mononuclear leukocytes obtained from symptomatic children infected with RSV frequently expressed viral antigens. Viral antigens appeared to be detected more frequently in cells from the younger subjects. The findings suggest that initial or early RSV infections in children include infection of circulating immunocompetent cells. It remains to be determined whether the described RSV-induced alterations in lymphocyte subpopulations contribute to recovery from and/or recurrence of RSV infections.