Binding of drugs can vary considerably. Therefore, binding of the calcium antagonist diltiazem was studied in protein solutions and in serum of healthy persons, patients with renal failure, patients with cirrhosis, patients with rheumatoid arthritis, patients with myocardial infarction, and intensive care patients. The effect of in vitro addition of some cardiovascular drugs (lidocaine, disopyramide, quinidine, and bupivacaine) on the binding of diltiazem in serum of healthy volunteers was also investigated. Diltiazem is bound as well to alpha 1-acid glycoprotein (AAG) as to albumin. In patients with renal failure, myocardial infarction, and rheumatoid arthritis and in intensive care patients, AAG concentrations are increased, and in the patients with myocardial infarction an increased binding of diltiazem is found. In patients with cirrhosis, AAG concentrations and diltiazem binding are decreased. In vitro addition of lidocaine, disopyramide, bupivacaine, or quinidine in concentrations between 5 and 100 micrograms/mL, before dialysis, decreases the binding of diltiazem; the displacing effect is most pronounced with bupivacaine.