The extent of propranolol protein binding was determined in three different age groups of healthy drug-free caucasian males. Volunteers selected for study were 6-15 years old, 25-36 years old and 68-76 years old. Ten milliliters of blood were obtained via venipuncture and collected in glass tubes from the subjects after an overnight fast. Binding determinations were performed by equilibrium dialysis using radiolabelled propranolol. Serum albumin and alpha 1-acid glycoprotein concentrations were determined in all subjects by radial immunodiffusion. The results obtained showed wide intersubject variability in the binding ratio of propranolol and serum concentrations of alpha 1-acid glycoprotein. Mean albumin serum concentration was found to be significantly lower in the elderly group as compared to the adult and pediatric groups (p less than 0.02). A positive correlation was found between the binding ratio of propranolol and the serum concentration of alpha 1-acid glycoprotein in all the subjects (r = + 0.66, p less than 0.005). No significant correlation was found between the binding ratio of propranolol and the serum concentration of albumin (r = -0.03, p less than 0.88). These data suggest that the extent of propranolol binding is influenced primarily by serum concentrations of alpha 1-acid glycoprotein and not by differences in age.