The response of subpopulations of peripheral venous blood lymphocytes to systemic bacterial or viral infections was studied. B-lymphocytes were defined by the presence of surface binding sites for mu chains, which were determined by immunofluorescent staining. T-lymphocytes were defined by the ability to form active sheep cell rosettes. Virus-infectible lymphocytes, which may represent activated T-lymphocytes, were defined by the ability to support virus replication. Patients with bacterial infections had an increase in the B-lymphocytes of peripheral venous blood, whereas patients with viral infections had an increase in T-lymphocytes as compared to controls. The number of virus-infectible lymphocytes was increased in patients with bacterial infections but not in patients with viral infections. These studies suggest that subpopulations of human peripheral blood lymphocytes vary in response to different types of infectious agents.