The authors evaluated the financial and health implications of treatment choices for three serious classes of infection: hospital-acquired pneumonia, intra-abdominal infection, and sepsis of unknown origin. Data were obtained from a systematic review of clinical literature and published data bases, by written questionnaire from a panel of infectious disease authorities, and from actual costs at a tertiary-care hospital. For pneumonia and sepsis, the third-generation cephalosporin evaluated (ceftizoxime) was found to be less expensive than other regimens, when costs of dose preparation and administration, monitoring, and toxicity were added to drug acquisition costs. The lowest-cost regimen for intra-abdominal infection was metronidazole plus gentamicin. Modest differences in efficacy would easily outweigh differences in toxicity, however, and could justify the use of more expensive regimens (e.g., mezlocillin plus gentamicin for hospital-acquired pneumonia, and cefoxitin plus gentamicin for intra-abdominal infection). If all regimens are assumed to be equally efficacious, then the third-generation cephalosporin was both lowest in cost and, owing to its low toxicity, greatest in net health benefit.