Spleen cells of C57BL/6 mice injected with corticosterone were compared with cells from mice injected with saline in their ability to respond to the mitogens PHA, Con A, and LPS. Both unseparated cells and cells separated into T-enriched and B-enriched fractions were studied. After either seven daily injections or four injections every other day of up to 100 mumoles hormone/kg body weight, the ability of both T and B cells to respond to mitogens was affected, the unseparated cells being more affected than the separated cells. In the whole spleen preparations, corticosterone seemed to inhibit the B cells more than the T cells, whereas when the cells were separated into T and B fractions, only the response of the cells in the T fraction was significantly reduced by the hormone. This suggests that this hormone may have a greater effect on the responsiveness of T cells than on B cells, whereas it reduces B cell number more than T cell number.