The disposition of a 25 mg single oral dose of desipramine was investigated in five rapid and four slow hydroxylators of debrisoquin before and during oral administration of 1200 mg cimetidine daily. AUC and elimination half-life of desipramine increased during cimetidine administration in rapid but not in slow hydroxylators. This was the result of a decrease in overall clearance. The urinary recovery of 2-hydroxydesipramine was significantly decreased in rapid hydroxylators during cimetidine administration. We conclude that cimetidine inhibits the metabolism of desipramine in rapid but not in slow hydroxylators.