A case report of dramatic increases in serum digoxin levels after alprazolam administration prompted our investigation. Twelve inpatients receiving long-term digoxin (0.25 mg daily) randomly received oral administration of either 1.0 or 0.5 mg alprazolam per day for 7 days. In each dosage group, three patients were older than and three were younger than 65 years of age. The area under the concentration-time curve for serum digoxin increased significantly in patients receiving 1 mg alprazolam daily, and this increase was more pronounced in patients older than 65 years of age. Clinical digoxin toxicity developed in one elderly patient who was receiving 1 mg/day alprazolam.