Cephaloridine, a semisynthetic derivative of cephalosporin C, was administered in single doses to mice, rats, guinea pigs, rabbits, cats, dogs, and monkeys. Acute LD50 values, obtained by various routes for mice, rats, and guinea pigs, were high. Rabbits, cats, dogs, and monkeys survived doses of 0.2 g/kg.Sublethal doses of the antibiotic damaged the proximal convoluted tubules of the kidneys of the mice, rats, guinea pigs, rabbits, and, probably, the monkeys. Tubular necrosis in mice was shown to be reversible. The relative sensitivities of the kidneys of various species were assessed by measurement of ND50 values (single doses producing histologic signs of kidney damage after 48 hours in 50% of animals).Sex differences in mortality and nephrotoxicity were observed in some species.Administered subcutaneously in large doses at high concentration, cephaloridine ulcerated the skin of mice and rats, but smaller doses were not irritant to the skin of guinea pigs or dogs. Cephaloridine was much less irritant to rabbit muscle than sodium penicillin G, and did not damage the veins of the mouse tail.Doses up to 25 mg/kg, administered intravenously to anesthetized cats, had no demonstrable pharmacodynamic effect.