Abstract Potential nephrotoxicity of cephaloridine and cephalothin was studied in rabbits and monkeys. Dose-related nephrotoxicity caused by cephaloridine, but not cephalothin, was demonstrated. Cephaloridine injections of 500 and 200 mg. per kilogram per day, intramuscularly, in rabbits and monkeys resulted in marked alteration in renal function and necrosis of proximal tubules; 100 and 50 mg. per kilogram per day doses did not appear to cause renal injury. Cephalothin injections in rabbits of 500 and 200 mg. per kilogram per day caused minimal swelling or hydropic changes in proximal tubular epithelium but no functional abnormalities. These data showed that dosages of cephaloridine exceeding 100 mg. per kilogram per day were nephrotoxic, whereas, cephalothin appeared to have much less nephrotoxic potential.