Sulfinpyrazone and phenylbutazone cause stereoselective alterations in the metabolic clearance of racemic warfarin in man. To determine if these drugs additionally displace warfarin from its binding sites in vivo free fractions of plasma warfarin were measured by equilibrium dialysis. Single doses of racemic warfarin, 1.5 mg/kgb.wt., were administered to eight normal humans. Six subjects received 300 mg orally of phenybutazone daily, beginning 3 days before warfarin and continuing throughout hypoprothrombinemia. Six subjects in separate experiments received 400 mg orally of sulfinpyrazone daily by the same schedule. Free warfarin of every subject's plasma was measure by equilibrium dialysis; trace amounts of [14C] racemic warfarin were added to each sample. The free fraction increased from 1.09% for warfarin alone to 1.46% (34%) during concurrent phenylbutazone (P less than .001). Free warfarin was unaltered by sulfinpyrazone, 1.08%. As the lack of effect of sulfinpyrazone on free warfarin enantiomorphs, the experiments were repeated with them. Sulfinpyrazone had no significant effect on the free fraction of either S-warfarin or R-warfarin. Sulfinpyrazone augmented the hypoprothrombinemia of racemic warfarin by steroselectively altering its metabolic clearance;phenylbutazone additionally displaced albumin-bound warfarin.