An open-label, randomized study was conducted to evaluate the safety and efficacy of cefepime versus ceftazidime in the treatment of severe bacterial infections, including septicemia, urinary tract infection, bacterial bronchitis, bacterial pneumonia, and intraabdominal infection. Fifty-two patients with severe infections were eligible and prospectively randomized to receive cefepime (26 patients) or ceftazidime (26 patients) during a 15-month period. Forty-two patients were evaluable (24 in the cefepime group and 18 in the ceftazidime group). Most (86%) of the patients had urinary tract infections and the most commonly isolated pathogen was Escherichia coli (79%). Satisfactory clinical response rates of 71% and 61%, and bacteriological eradication rates of 87.5% and 89% were achieved for the cefepime and ceftazidime groups, respectively. Two patients treated with cefepime died, one from superinfection and one from suspected paraneoplastic syndrome. Cultures of the blood obtained at entry into the study were positive in 19 (45%) of the 42 evaluable cases. In the cefepime group, a patient with Salmonella paratyphi A septicemia was cured, which has not been previously reported. Adverse effects attributable to therapy were minimal in both groups of patients, and none required discontinuation or dose reduction. In conclusion, these results suggest that cefepime is as efficacious and well tolerated as ceftazidime in the treatment of severe bacterial infections, such as septicemia, urinary tract infection, bacterial bronchitis, bacterial pneumonia, and intraabdominal infection.