Diltiazem binding was measured by equilibrium dialysis in the serum of five healthy male subjects, aged 22 to 34 years, at seven serum diltiazem concentrations ranging from 0.03 to 2.06 micrograms/ml. The percentage of unbound diltiazem ranged from 19.6 +/- 3.1 to 22.6 +/- 4.1 (mean +/- S.D.) and was independent of serum diltiazem concentration. Serum diltiazem binding was also examined in the presence of six drugs that might be used concurrently with diltiazem in patients being treated for cardiac disease. The percentage of unbound diltiazem was not influenced by digoxin, hydrochlorothiazide, phenylbutazone, propranolol, salicylic acid, or warfarin at therapeutic concentrations of these drugs over the therapeutic range of diltiazem.