The serum protein binding of phenytoin, diazepam and propranolol was investigated in vitro in 32 elderly people with an age-related decrease in renal function by a pressure ultrafiltration method at 37 degrees C. The mean age of the patients was 88 +/- 1 years (mean +/- SE), and their mean 51Cr-EDTA clearance 46 +/- 4 ml/min. The main reason for hospitalization of these patients was their age. The free fraction of phenytoin correlated negatively with the serum albumin concentration, and that of propranolol with the alpha 1-acid glycoprotein (alpha 1-AGP) concentration. The free fraction of diazepam did not correlate with either of these binding proteins. In stepwise multiple regression analysis, the most significant variable for phenytoin free fraction was serum albumin concentration, with the serum urea concentration coming in second place. For the diazepam free fraction, the only significant variable was the serum urea level, although in the correlation matrix the correlation with creatinine was also significant. When the effect of serum albumin level was corrected mathematically, the urea level was the best determinant in regression analysis for both the phenytoin and diazepam free fractions. It can be concluded that an age-dependent decrease in renal function increases the free fraction of phenytoin and diazepam and is, together with hypoalbuminaemia, responsible for the increased free fraction of these drugs in the elderly. For propranolol the only important factor is the serum alpha 1-acid glycoprotein concentration.