The effects of chronic treatment with allopurinol and clofibrate on the elimination from plasma of warfarin and dicoumarol were examined in man. In addition, the binding of warfarin to human serum proteins was measured with and without clofibrate and its metabolite chlorophenoxyisobutyric acid (CPIB), both present in therapeutic concentrations. Treatment with allopurinol and clofibrate did not alter the rate of elimination of warfarin from plasma. In addition, clofibrate and CPIB caused no significant displacement of warfarin from serum proteins. This evidence supports the conclusion that the clinically significant potentiation of warfarin activity by clofibrate in man is due to an interaction at the receptor site. In contrast, treatment with allopurinol resulted in significant prolongation of the plasma half-life of dicoumarol in one of three subjects. These data are consistent with inhibition of the metabolism of dicoumarol by allopurinol in some individuals.