The activity of cefoxitin was compared with that of cephalothin against 229 bacterial strains. Cefoxitin was more active against most Gram-negative strains, notably against indole-producing Proteus spp., which are usually resistant to the cephalosporins. Cefoxitin was not susceptible to any significant extent to degradation by beta-lactamases produced by Gram-negative organisms. Against Gram-positive organisms, however, cefoxitin was considerably less active than cephalothin, but minimum inhibitory concentrations for Staphylococcus aureus were well within therapeutically attainable blood levels.Pharmacokinetic studies in 18 volunteers showed a higher and longer sustained antibiotic activity in serum and urine after injections of cefoxitin than after equal doses of cephalothin. Urinary recovery of cefoxitin activity was also much higher than that of cephalothin. No evidence of toxicity due to cefoxitin was found. Cefoxitin was slightly less painful after intramuscular injection than cephalothin.