The in vitro activity of cefepime was compared versus that of 10 antimicrobial agents commonly used in the treatment of serious infections caused by common aerobic gram-negative bacteria: aztreonam, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, ticarcillin-clavulanic acid, and tobramycin. We tested 30 clinical isolates representing a cross section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa collected at our tertiary-care university hospital. The most potent beta-lactams were imipenem and cefepime, which demonstrated significant activity against the majority of strains in all 3 genera of bacteria tested, as did ciprofloxacin and tobramycin. Ceftazidime was active against Pseudomonas aeruginosa but was less potent against Klebsiella and Enterobacter spp. Cefoperazone and ceftriaxone were less active than ceftazidime against Pseudomonas aeruginosa. Cefepime was found to be highly active against many resistant organisms that traditionally have been difficult to treat.