An assay was developed for studying the effect of age on human colony-forming T and B cells. Phytohemagglutinin was used to induce the formation of T cell colonies and anti-human Fab antibodies were used to induce the formation of B cell colonies. The assay requires a short ( < 8 h) incubation in liquid media in the presence of a mitogen prior to plating in semisoft agar. Neither autologous serum, red cells, nor conditioned media are required to support colony formation. The kinetic and morphologic characteristics of T and B cell colonies were different. Formation of T cell macro- but not microcolonies was significantly impaired during aging. Formation of B cell colonies was decreased with aging, but the decrease was not significant.