We compared the in-vitro activity of cefoperazone-sulbactam (2:1), other beta-lactams, amino-glycosides and ciprofloxacin against cefoperazone-susceptible and -resistant nosocomial gram-negative bacilli. Resistant isolates including Pseudomonas aeruginosa were susceptible to cefoperazone-sulbactam; the susceptible isolates had modestly increased susceptibility to the combination. Sulbactam, by itself, was poorly active. Among others tested, ciprofloxacin and imipenem were the most active. No inoculum effect was seen with cefoperazone-sulbactam and this drug combination had a prolonged post-antibiotic effect. Cefoperazone-sulbactam is an attractive candidate for evaluation in the treatment of nosocomial infections due to aerobic gram-negative bacilli.