OBJECTIVE: A warfarin-baclofen interaction has been postulated, but has not been documented in the literature. The purpose of this study is to investigate the drug interaction between warfarin and baclofen in rats. METHOD: Twenty Sprague-Dawley rats (250-300 gm), divided into a control and a study group were used. 0.02 mg/day of warfarin was administered intraperitoneally without baclofen for the first three days. Daily blood samples were drawn after six hours of warfarin adminstration for measurement of prothrombin time (PT) and International Normalized Ratio (INR). On the fourth day, the rats in the study group were given 0.02 mg of warfarin and 0.6 mg of baclofen intraperitoneally. For the control group, 0.02 mg of warfarin was administered on all four days. PT and INR measurements were taken at 3 hours, 6 hours, and 24 hours after the administration of warfarin with or without baclofen. RESULTS: Mean INR value was significantly increased by concomitant baclofen administration after 6 hours, resulting in 1.72 for the control group with warfarin alone and 2.74 for the study group with warfarin and baclofen (p<0.05). CONCLUSION: The concomitant administration of warfarin and baclofen affects the anticoagulant effect of warfarin. Physicians should be aware of the risk for increased anticoagulant effect of warfarin when baclofen is also administered.