In acute as well as chronic renal insufficiency significant immunological abnormalities were found: diminution of delayed hypersensitivity skin reactions, lymphopenia, reduction of the absolute but not relative number of peripheral blood T-lymphocytes. Responses of lymphocytes from uremic patients to PHA, allogeneic cells, or antigens were normal when lymphocyte cultures were preformed in allologous serum from a healthy individual. Sera from uremic patients had an inhibitory or toxic effect on stimulation of normal lymphocytes. Such an in vitro inhibitory activity was found not only in the whole serum but also when certain substances retained in renal failure (methylguanidine, larger molecules, etc.) were added in the lymphocyte cultures.