An experimental model in rats was developed to define the nature of humoral and cellular factors that contribute to impaired immune responsiveness in chronic renal failure. Addition of uremic rat serum to both normal and uremic lymphocytes significantly suppressed cellular responses, the suppression being more pronounced with uremic lymphocytes. Lymphocytes from uremic rats were only marginally less responsive than normal lymphocytes to concanavalin A stimulation when normal rat serum was added to the cultures, indicating that the cellular factors in impairment were less important than humoral ones. Antibody formation in rat splenocyte cultures to bovine serum albumin was suppressed by addition of uremic serum, but the response to sheep erythrocytes was unaffected. Thus the effect on antibody response in uremic animals is dependent upon the antigen tested.