OBJECTIVE: The aim of this study was to examine the impact of a rationalized antibiotic prescription program in a 600-bed hospital. PATIENTS AND METHODS: The program was based on a local consensus policy, developed with the prescribers themselves, together with individual nominative dispensing (IDN) of the most costly antibiotics, and training/information programs aimed at institutional prescribers. The impact of the program was assessed in terms of the relevance of prescriptions (6-monthly audits), changes in the overall cost of anti-infectives, the average daily cost per hospital patient, and changes in the pattern of antimicrobial resistance among pathogens isolated in the institution. RESULTS: Reference recommendations were established for most clinical settings encountered in the hospital (104 for adults, 78 for children). The four audits conducted since June 1996 show that the rate of unjustified prescriptions has remained below 6%. The cost of antimicrobials has fallen regularly, both in absolute terms and as a proportion of total drug costs. Finally, resistance rates among the different pathogens studied have fallen or remained stable. CONCLUSION: Rationalization of antimicrobial chemotherapy in a short-stay hospital necessitates an institution-based policy with long-term objectives, a large initial investment and, above all, a participative approach among all prescribers.