Two dosing regimens of cefoperazone plus mezlocillin were compared in a prospective, randomized trial for therapy of febrile cancer patients. The two regimens were 5 g mezlocillin plus 2 g cefoperazone intravenously every four hours (higher dose) or 3 g mezlocillin plus 1 g cefoperazone intravenously every four hours (lower dose). Although the overall response rate was higher with the higher dose regimen (78 percent versus 66 percent, p = 0.04), the two regimens were comparable in patients with documented infections (72 percent versus 68 percent). Likewise, the two regimens were equally effective against those infections in which the pathogen could be determined (82 percent versus 82 percent). Serum bactericidal titers of at least 1:32 against a known pathogen were associated with a higher response rate than were titers of less than 1:32, but the higher dose regimen did not result in higher serum bactericidal titers. Hypoprothrombinemia was a side effect, especially with the higher dose regimen, before prophylactic vitamin K was routinely administered to patients. Since there were no major benefits with the use of the higher dose regimen of mezlocillin plus cefoperazone, the lower dose regimen is more appropriate for routine usage.