Antigenic stimulation of athymic mice on the BALB/c background by infection with the pinworms Aspiculuris tetraptera and Syphacia obvelata or by xenografts of human tumors induced a proliferation of T- and B-lymphocytes in spleen and lymph nodes and occasional germinal center formation. The proliferating T-lymphocytes showed greater fluorescence per cell than the Thy 1-positive cells from unstimulated athymic mice when examined by cytofluorography using anti-Thy 1 antiserum. The proliferating T-lymphocytes were shown to be functional by their ability to help mount an in vivo antibody response to sheep erythrocytes and other thymus-dependent antigens. Spleen cells cultures taken from mice at early stages of antigenic stimulation responded in vitro to the thymus-dependent mitogens concanavalin A and phytohemagglutinin. However, spleen cell cultures taken from mice chronically stimulated by foreign antigens were apparently already maximally stimulated and showed no further stimulation when incubated with concanavalin A or phytohemagglutinin in vitro.