The in vitro activity of norfloxacin (MK366) against 477 aerobic gram-negative and gram-positive clinical isolates was compared to that of nalidixic acid, nitrofurantoin, ampicillin, cephalexin, trimethoprim, sulfamethoxazole, and the combination trimethoprim-sulfamethoxazole. Norfloxacin was more active than the other agents against all gram-negative organisms tested. Minimal inhibitory concentrations (MICs) of Pseudomonas aeruginosa were less than or equal to 0.125-32 mg/l with 90% inhibited (MIC90) by 4 mg/l; MICs of the Enterobacteriaceae including Serratia marcescens were less than or equal to 0.125-8 mg/l with an MIC90 of less than or equal to 4 mg/l. There was also excellent activity against the gram-positive cocci including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus and the enterococci, with MICs less than or equal to 0.125-4 mg/l and an MIC90 less than or equal to 4 mg/l. Only 8 of 477 organisms were norfloxacin-resistant (MIC greater than or equal to 16 mg/l): 3 of 100 Pseudomonas aeruginosa, 3 of 10 Pseudomonas maltophilia and 2 of 15 Streptococcus bovis strains. In contrast, 97% of the gram-positive cocci and 49% of the gram-negative bacilli were nalidixic acid-resistant (MIC greater than or equal to 32 mg/l). Norfloxacin shows excellent activity against a wide range of bacteria and merits further study as a urinary antibacterial agent.