Decreased plasma binding of phenytoin and diazepam has previously been described in patients with alcoholic liver diseases. It has been attributed to hypoalbuminemia, endogenous displacers and/or qualitative changes in albumin such as formation of adducts with acetaldehyde, a highly reactive metabolite of ethanol. In the present report this hypothesis was tested. After treating the sera with activated charcoal to remove the endogenous displacers and adjusting albumin concentration to a constant level, the binding parameters of both drugs, phenytoin and diazepam, were determined in 14 healthy men and 16 alcoholic patients by equilibrium dialysis. In these conditions, no significant difference in the number of binding sites nor in the affinity constant was observed, which suggests that acetaldehyde adducts with proteins do not contribute, to a major extent, to the defect of drug binding observed in alcoholic patients.