A therapeutic interchange program based on microbial patterns within an institution is described. A change in anaerobic susceptibility patterns, increased prevalence of enterococcal infections, and cost factors provided the rationale for the therapeutic interchange of ampicillin-sulbactam for cefoxitin. Ampicillin-sulbactam was recommended for prophylaxis in intraabdominal or gynecological surgery as well as for treatment for gynecological infections. Cefoxitin was restricted to penicillin-allergic patients and women who were pregnant or breast-feeding. The transition from cefoxitin to ampicillin-sulbactam proceeded smoothly as a result of preliminary education of pharmacists and physicians. Pharmacists participated in continuing-education programs and received concise guidelines for the interchange and follow-up instructions; physicians learned of the program from the drug newsletter published by the pharmacy department. Three months after the program began, only one physician was resistant to the interchange. After the program began, 11 antimicrobials, including cefoxitin, were used less frequently and ampicillin-sulbactam use increased. No adverse clinical consequences from the interchange were detected. A therapeutic interchange program based on institution-specific microbial patterns and educational efforts by the pharmacy department produced a change in physician prescribing.