Thirty-one patients with severe gram-negative bacterial infections were treated successfully with a combination of cefamandole nafate plus gentamicin or tobramycin. The patients were divided into two treatment groups: group 1 received low-dose therapy (80--100 mg of cefamandole nafate/kg per 24 hr plus 3 mg of either gentamicin or tobramycin/kg per 24 hr), and group 2 patients, who had suspected bacteremia, received high-dose therapy (170 mg of cefamandole nafate/kg per 24 hr plus 5 mg of either gentamicin or tobramycin/kg per 24 hr). All of the patients were clinically and bacteriologically cured of their primary infections. All four episodes of bacteremia were cleared within 24 hr after therapy was initiated. There was a uniform decrease in the rate of creatinine clearance which was slightly greater in group 2 patients; however, all creatinine clearance values were within the normal range and actually improved during therapy. There was no difference between the clearance values of the tobramycin-treated patients and gentamicin-treated patients. A few transient abnormalities in results of liver function tests occurred during the study. In one patient whose serum was positive for hepatitis-associated antigen, the alkaline phosphatase, aspartate aminotransferase, and bilirubin values were elevated on admisssion of the patient to the hospital, increased fivefold during therapy, and decreased to the base-line admission values six days after therapy; however, it is difficult to establish that this reaction was antibiotic-induced hepatic toxicity.