The antibacterial activity of ciprofloxacin (Bay o 9867) was compared with those of norfloxacin, nalidixic acid, trimethoprim-sulfamethoxazole, cefaclor, sisomicin and cefotaxime in in vitro and mouse protection studies. Approximately 300 clinical isolates of clinically important gram-positive and gram-negative species were used. The median MICs of ciprofloxacin against gram-positive and gram-negative bacteria ranged from 0.015–1 mg/l. Ciprofloxacin was 2–8 fold more active than norfloxacin and 100-fold more active than nalidixic acid. It also had a wider spectrum of activity against gram-positive organisms including even enterococci. No cross-resistance was observed between ciprofloxacin and-lactam antibiotics or aminoglycosides. Only acidic pH conditions decreased its activity. Ciprofloxacin showed rapid bactericidal action against organisms in both the logarithmic and stationary growth phases. In mouse protection studies (intraperitoneal infection) ciprofloxacin was significantly more effective than norfloxacin, ampicillin, trimethoprim-sulfamethoxazole, and also showed excellent activity againstPseudomonas infections.