The in vitro activity and beta-lactamase stability of 7-[d(-)-alpha-(4-ethyl-2,3-dioxopiperazino-carbonylamino) -p-hydroxyphenylacetamido]-3-[(1-methyl)-5-tetrazolylthiomethyl] -Delta(3)-cephem-4-carboxylic acid (cefoperazone), a cephalosporin analog of piperacillin, were compared with the activities and stabilities of other cephalosporins and cephamycins. The compound was less active than cephalothin or cefamandole in inhibiting Staphylococcus aureus; it was as active as cefamandole and cefoxitin against most of the Enterobacteriaceae but less active than cefotaxime. It was more active than carbenicillin or piperacillin against Pseudomonas aeruginosa. In general, the compound was not active against Bacteroides. It was hydrolyzed by the beta-lactamases of some Escherichia coli which hydrolyzed cefamandole, but was stable to most plasmid-mediated, chromosomally mediated, inducible beta-lactamases in the Enterobacteriaceae and Pseudomonas.