Protein binding of disopyramide, binding capacities, affinity constants and serum concentrations of alpha 1-acid glycoprotein (AAG) were studied in five groups of patients. A: young healthy volunteers (n = 8); B: elderly patients with minor symptoms of ischaemic heart disease (n = 9); C: patients with cirrhosis of the liver and normal values of coagulation factors (II, VII and X), albumin and immunoglobulin G (n = 8); D: patients with cirrhosis and at least two abnormal of the previously mentioned values (n = 9) and E: eleven patients with severely impaired renal function. Subfractions of AAG (Fr1, Fr2 and Fr3) were determined by affinoimmunoelectrophoresis. AAG concentration was significantly (P less than 0.005) elevated in group E patients and decreased (P less than 0.025) in group D patients. Fr2 is probably associated with the high affinity, first binding site of disopyramide to AAG. Earlier observations of a reduced qualitative binding of disopyramide in patients with cirrhosis can be explained by a significant decrease in Fr2 (P less than 0.001) in group D patients. The protein binding of disopyramide in patients with uraemia was significantly increased due to a significant (P less than 0.005) increase in AAG concentration in spite of a smaller (P less than 0.025) affinity constant. Suggestions for therapeutic drug monitoring based on total serum concentrations are given.