Three newer cephalosporins (cefamandole, cefoxitin and cefazaflur) were investigated, in comparison with three older agents (cephalothin, cephaloridine and cefazolin) to determine their stability to beta-lactamases of gram-negative bacilli, and to correlate this with their antibacterial activity. Nine of the 17 bacterial strains employed produced broadspectrum beta-lactamases; the remaining eight produced cephalosporinases. The cephalosporins were highly active against bacteria producing broad-spectrum beta-lactamases; they were less active against organisms producing cephalosporinases. All of the cephalosporinase-producing strains were resistant to cephalothin anc cephaloridine. With the other cephalosporins the correlation between hydrolysis by cephalosporinases and resistance of the organisms was poor. Four to eight cephalosporinase-producing strains were resistant to cefoxitin, which was completely resistant to hydrolysis by the beta-lactamases. Cefozolin, cefamandole and cefazaflur inhibited several of these strains in spite of destruction by the beta-lactamase. Several cephalosporins need to be used in antimicrobial susceptibility testing of gram-negative bacilli.