A significant drug interaction between verapamil and digoxin, resulting in elevated serum digoxin concentrations, has been well documented in the medical literature. However, a similar interaction between digoxin and the calcium channel blockers nifedipine and diltiazem has not been conclusively established. This study investigated the influence of diltiazem hydrochloride on trough serum concentrations of concurrently administered digoxin in eight healthy volunteers. During the control phase of the study, volunteers were administered digoxin 0.25 mg/d for 13 days, and subsequently judged to be at steady state by serial determinations of digoxin serum concentrations. Twenty-four hour urine collections were done for creatinine clearance and urinary digoxin clearance determinations. Phase II of the study involved the addition of diltiazem hydrochloride 30 mg qid to the on-going, daily regimen of digoxin. After 14 days of concomitant therapy, steady-state trough digoxin concentrations were again determined, as well as creatinine clearances and urinary digoxin clearances. This investigation demonstrates that concomitant administration of diltiazem hydrochloride with digoxin results in significantly elevated steady-state trough digoxin concentrations (0.32 +/- 0.07 ng/ml increasing to 0.48 +/- 0.06 ng/ml, p less than 0.01). Urinary digoxin clearance decreased from 223.5 +/- 35.7 ml/min to 153.4 +/- 17.5 ml/min (p less than 0.05). Creatinine clearances were unaltered. A review of the current literature on this topic is included.