The susceptibility of 4,929 unselected clinical isolates of bacteria to cefoxitin and cephalothin was determined by the single-disk method, using a computer-associated electronic zone analyzer to obtain, record, and process measurements of sizes of zones of inhibition. Both cefoxitin and cephalothin were effective against most gram-positive strains, including Staphylococcus aureus, S. epidermidis , micrococci, and all streptococci except enterococci. The three strains of Listeria monocytogenes tested were susceptible to cephalothin but resistant to cefoxitin. There was little difference between the cefoxitin and cephalothin susceptibility of Salmonellae, Citrobacter sp., Enterobacter sp., Proteus mirabilis , and Pseudomonas sp. Cefoxitin was more effective then cephalothin against Escherichia coli, Klebsiella sp., Serratia sp., indole-positive Proteus sp., Providence sp., Flavobacter sp., Herellea vaginicola , and Mima polymorpha . Cefoxitin also appeared to exhibit enhanced activity, as compared with cephalothin, against Bacteroides sp. Thus cefoxitin appears to have a very broad antibacterial spectrum which is greater than that of cephalothin, especially against gram-negative strains.