Ciprofloxacin plus azlocillin have been shown to exhibit in vitro synergy versus a variety of organisms, including Pseudomonas aeruginosa. This study examined this interaction in vivo, testing serum bactericidal activity (SBA) in six healthy male subjects after intravenous administration of ciprofloxacin 4 mg/kg (C), azlocillin 60 mg/kg (A), and the two simultaneously (C/A). Eight different organisms were tested: four isolates of P. aeruginosa with varying susceptibilities to C and A, and one isolate each of Escherichia coli (EC), Staphylococcus aureus (SA) Serratia marcescens (SM), and Klebsiella pneumoniae (KP), all of which were susceptible to both drugs. Blood samples were collected at the end of 30-min infusions and at 4 and 8 hr. Reciprocal titers were plotted versus time and area under the bactericidal titer curve (AUBC) calculated to assess antibacterial interactions. Results indicated that P. aeruginosa-1 (PA-1), EC, and KP were synergistically killed by C/A. AUBC for PA-1 were C = 36, A = 11, C/A = 144, p less than 0.05. AUBC for EC were C = 1059, A = 180, C/A = 1504, p = 0.05. AUBC for KP were C = 327, A = 97, C/A = 584, p = 005. Additive effects were demonstrated versus all of the other organisms except Serratia marcescens, where an indifferent effect was observed. Ciprofloxacin plus azlocillin may be a useful combination of the treatment of selected Gram-negative bacillary infections.