The aim of this study was to investigate whether serum protein binding of drugs is altered in patients with severe chronic cardiac failure. A total of 27 patients of the cardiac unit participated in the study. One group comprised 15 subjects with chronic cardiac failure (grade III-IV according to the New York Heart Association); 12 patients served as controls (grade I-II). The extent of binding was determined in the therapeutic concentration range by means of equilibrium dialysis at pH 7.4 and 37 degrees C. The binding of six marker drugs shows no difference between controls and patients with chronic cardiac failure. Furthermore, measured free fractions were in the range reported in the literature for healthy, untreated individuals. Our selection of drugs comprised substances that are representative of the three major drug-binding sites on human albumin (diazepam-digitoxin-warfarin/phenytoin). Furthermore, propranolol and imipramine represent examples of drugs binding mainly to lipo- and glycoproteins. The results suggest that the binding of most drugs encountered in clinical practice will be unchanged in patients with chronic cardiac failure.