We examined the impact of a rational antibiotic prescription programme based on a multidisciplinary consultative approach in a 600-bed hospital. The programme involved four measures: (1). drawing up of a local prescribing consensus with all prescribers; (2). a restricted prescriptions policy for the most expensive antibiotics; (3.assessment of the prescription of these antibiotics by regular audits; and (4). institutional training and information for prescribers. The impact of the programme was assessed by comparing actual prescriptions with the criteria of the local consensus, compliance with the restrictive prescription policy, changes in the average daily cost of antibiotic therapy per inpatient and changes in the local ecology of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae producing extended-spectrum beta-lactamases (EPESB) and ceftazidime-resistant Pseudomonas species (CRP). Using a participatory consensual approach, 182 reference recommendations were established (104 for adults, 78 for children), corresponding to 85% of the clinical settings encountered in the hospital. Six audits, conducted since June 1997, show that the rate of unjustified prescriptions first fell significantly (from 6 to 0%, P<0.001), then increased significantly (from 0 to 3%, P<0.05) before stabilizing at 3%. The cost of antimicrobials per inpatient day fell significantly (from US dollars 13.8 in 1997 to US dollars 11 in 2000, P<0.001). The prevalence of MRSA and CRP remained stable, while that of EPESB fell significantly (P<0.001). This multidisciplinary consultative approach thus reduced antibiotic costs, contributed to infection control, and improved the quality of antibiotic prescription.