Results are reported for agar dilution susceptibility testing of 3,075 isolates of aerobic bacteria collected from >200 U.S. institutions, located in 30 different states. These isolates were collected from 1987 through 1991 from patients who participated in cefepime clinical trials. Cefepime susceptibility was compared with ceftazidime, cefotaxime, ceftriaxone, cefoperazone, and imipenem. To avoid duplication of strains, only initial isolates were included. Cefepime minimum inhibitory concentration (MIC90) values for Enterobacteriaceae were < or = 0.5 microg/mL, except for two species, Citrobacter freundii and Providencia stuartii, with MIC90 values of 2 and 1, respectively. The MIC90 values of the other cephalosporins were higher, especially for Enterobacter aerogenes and C. freundii. The MIC90 values of cefepime for methicillin-susceptible Staphylococcus aureus (4 microg/mL) and Pseudomonas aeruginosa (8 microg/mL) were similar to those of cefotaxime for S. aureus (4 microg/mL), and to ceftazidime for P. aeruginosa (8 microg/mL). Streptococcus pneumoniae was similar in susceptibility to cefotaxime at 0.06 microg/mL. The activity of cefepime against a diverse group of gram-positive and gram-negative (1987-1991) bacteria isolates demonstrates the excellent activity of cefepime compared to third-generation cephalosporins and imipenem, particularly among C. freundii and E. aerogenes isolates, which were often resistant to other cephalosporins.