Sera of volunteers receiving ceftazidime (2 g) or amikacin (500 mg), alone or in combination, or cefoperazone (2, 4, or 6 g) or cefoperazone (2 g) with amikacin (500 mg) were evaluated for bactericidal activity against Klebsiella pneumoniae and Pseudomonas aeruginosa. Serum bactericidal activities were similar for ceftazidime and ceftazidime plus amikacin, but were definitely lower for amikacin alone. Against P. aeruginosa, a 6-g dose of cefoperazone resulted in a higher frequency of peak serum bactericidal activities greater than or equal to 1:8 than a 2-g dose of cefoperazone plus amikacin. Killing studies, performed in 1:8 diluted serum, demonstrated a higher killing rate for cefoperazone plus amikacin than for a 6-g dose of cefoperazone, the more resistant P. aeruginosa excepted. Emergence of resistance was found with a 2-g dose of cefoperazone for K. pneumoniae and with a 6-g dose of cefoperazone for P. aeruginosa, but not with cefoperazone plus amikacin.