Abstract Eighty subjects in whom there was no therapeutic indication for anticoagulant therapy were given four prothrombinopenic agents, bishydroxycoumarin, diphenadione, phenindione and warfarin. The onset of action of all four drugs was between the eighth and sixteenth hour following the administration of a single large dose. The peak effect for phenindione was obtained in thirty-two hours, and for the other three drugs in forty hours. The extent of depression was reasonably uniform among subjects receiving the same drug but the duration of effect was quite variable. The findings suggest that an induction program consisting of a single large loading dose followed by a maintenance dose might be practical and safe for all four drugs.