This study compared the efficacy of therapy with the double beta-lactam combination of ceftazidime plus piperacillin with that of single-agent therapy with ceftazidime, piperacillin, or amikacin alone and with that of two aminoglycoside-beta-lactam combinations against Pseudomonas aeruginosa peritonitis and bacteremia in neutropenic rats. Rats made severely granulocytopenic with cyclophosphamide became bacteremic secondary to peritonitis which was induced by intraperitoneal challenge with P. aeruginosa. Antibiotic therapy with single agents (amikacin, 20 mg/kg of body weight, intramuscularly; ceftazidime, 20 mg/kg of body weight, subcutaneously; piperacillin, 200 mg/kg of body weight, intramuscularly) or with the various combinations of agents was begun 2 h after bacterial challenge and was continued every 6 to 8 h for 62 h. Therapeutic efficacy was judged on the basis of survival 72 h after bacterial challenge, rate of mortality, incidence of bacteremia, and the emergence of resistant organisms. Based on these criteria, therapy with the double beta-lactam combination had no advantage over single-agent therapy and was in all cases clearly inferior to beta-lactam-aminoglycoside combinations.