A study of the susceptibility to cefotaxime and six other cephalosporins in 213 nonselected strains of nine different bacterial species clearly showed that cefotaxime was the most active against aerobic gram-negative bacilli. The same pattern emerged with 84 cephalothin-resistant strains of five enterobacterial species, but the mean minimal inhibitory concentration values for all cephalosporins were about twofold higher in this group of strains. Cephalothin was the most active antibiotic against Staphylococcus aureus. The inoculus effect of 10 cephalothin-resistant strains was relatively small, but it was most marked for cefamandole, as compared with that of three other new cephalosporins, including cefotaxime. The susceptibility of these cephalosporins to beta-lactamases from 12 beta-lactamase-producing enterobacterial strains was determined. Half of these were slightly active against cefotaxime and had similar activity against cefuroxime. Cefoxitin was not degraded at all, and cefamandole was the most susceptible. No correlation between beta-lactamase susceptibility and minimal inhibitory concentration values of different cephalosporins was found. Cefotaxime combined high intrinsic antibiotic activity with marked resistance to beta-lactamase inactivation.