OBJECTIVE: To determine whether an educational program featuring a drug cost manual can assist physicians in reducing their patients' out-of-pocket prescription drug expenses. DESIGN: Prospective controlled trial. SETTING: A general internal medicine-teaching clinic in a university hospital. PARTICIPANTS: Fifty-one medical interns. INTERVENTION: Thirty-one interns received a manual of comparative drug prices annotated with prescribing advice, two feedback reports, and weekly cost-oriented prescribing reminders. A control group concurrently participated in a manual-based educational program on cholesterol management. MEASUREMENTS: Copies of 3012 prescriptions written over 8 months were analyzed. MAIN RESULTS: Intervention group physicians prescribed less expensive drugs within classes of drugs. The change in drug price score per prescription was -0.15 (95% Cl, -0.27 to -0.04; P = 0.01). A score of 3 was assigned to the most expensive, 2 was assigned to intermediate-priced, and 1 was assigned to the least expensive drug or drugs in the class. An increase of 0.74 months' (Cl, 0.49 to 0.98; P less than 0.001) supply of medication was dispensed per prescription, reducing dispensing fees. The program was well accepted by the physicians. CONCLUSION: This relatively simple educational intervention can help physicians to reduce their patients' drug expenses and may serve as a model for incorporating cost information into the routine practice of medicine.