The relationship between binding ratio of imipramine and plasma alpha 1-acid glycoprotein (AAG) was determined in normal subjects, patients with chest pain syndrome, and patients after myocardial infarction. Binding ratio of imipramine was determined by equilibrium dialysis and plasma AAG concentration was determined by radial immunodiffusion. Plasma AAG concentrations ranged from 56 to 80 mg/dl (mean = 65 +/- 9 mg/dl) in 12 normal subjects, from 86 to 228 mg/dl (mean = 125 +/- 37 mg/dl) in 12 patients with chest pain syndrome, and from 78 to 350 mg/dl (mean = 181 +/- 69 mg/dl) in 12 patients after myocardial infarction. Plasma AAG concentrations in the three patient groups differed. Binding ratio ranged from 5.6 to 19.8 (mean = 12 +/- 3.5). Binding ratio of imipramine significantly correlated with plasma AAG concentration, but not with plasma albumin. In addition, binding ratio of imipramine and pure AAG was significantly related, indicating AAG is an important determinant for imipramine binding. If plasma AAG concentration increases or changes rapidly, plasma drug concentration and drug effect may be unpredictable. Under these circumstances an estimate of free drug fraction may be clinically helpful and can be estimated from the formula. y = 7.95 + 0.03 X AAG.