Cefoperazone plus tobramycin was compared in a prospective, randomized trial with our standard regimen of ticarcillin plus tobramycin as empiric therapy of fever in granulocytopenic patients with cancer. Patients who received cefoperazone were also given vitamin K (5 mg orally twice a week). Of 39 microbiologically and clinically documented infections treated with ticarcillin plus tobramycin, 28 (72 percent) showed improvement. Of 27 microbiologically and clinically documented infections treated with cefoperazone plus tobramycin, 21 (78 percent) showed improvement. The overall response rates were similar (40 of 53, or 74 percent, for ticarcillin plus tobramycin versus 38 of 48, or 79 percent for cefoperazone plus tobramycin). There was no difference in response between groups according to site of infection. Serious side effects were minimal with both regimens. There were no enterococcal superinfections in patients receiving cefoperazone. These results suggest that the overall efficacy and toxicity of study regimens are similar.