Glutethimide, amobarbital, secobarbital, and meprobamate—drugs commonly used in humans—markedly reduce the warfarin plasma half-life (T½) in dogs. Addition of such drugs increases the warfarin required for maintenance of adequate anticoagulation. Withdrawal of these drugs from persons previously receiving anticoagulants could lead to severe bleeding. Clofibrate prolongs the warfarin plasma T½ in dogs. Administration of clofibrate to adequately anticoagulated animals precipitates hemorrhage. Effects of the addition or withdrawal of any drug to the therapeutic regimen of patients receiving oral anticoagulants must be carefully monitored with frequent prothrombin time determinations.