Ninety-four cases of pyelonephritis including 20 who had concurrent bacteremia were treated with cefamandole alone or in combination with either gentamicin or tobramycin. Doses of cefamandole ranged from 1--2 g by intermittent intravenous (VI) infusion every 4 to 8 h; gentamicin and tobramycin doses ranged from 1--1.7 mg/kg every 8 h also by intermittent IV infusion. Duration of therapy ranged from 5 to 23 days (mean 7.3 days). Both single and combination therapy successfully treated acute pyelonephritis and bacteremia in all patients. Seven strains of E. coli and one of Klebsiella pneumoniae responsible for initial infection were resistant to cephalothin but sensitive to cefamandole. Relapse with cefamandole sensitive bacteria occurred in 27% of patients receiving only cefamandole and 8% of those patients receiving combination therapy. Reinfection with cefamandole resistant organisms, predominantly Pseudomonas aeruginosa occurred in five patients. One patient had an intrarenal abscess due to E. coli which was successfully treated with 23 days of cefamandole. One patient died. However, death was due to acute pulmonary embolism, not infection. None of the patients receiving cefamandole plus gentamicin or tobramycin experienced a significant decrease in creatinine clearance during or after therapy. Skin rash, mild thrombophlebitis at the IV site and transient elevation of alkaline phosphatase and SGOT were the only side effects noted.