Monotherapy with Ketanserin, a serotonin receptor antagonist, reduces blood pressure in a sizeable number of patients with essential hypertension. The present study was designed to compare its antihypertensive potency with those of metoprolol in a double-blind treatment and further to study its long-term efficacy and safety in a one-year open trial, alone or combined to metoprolol, according to diastolic blood pressure (DBP) normalization. Twenty-four patients with mild to moderate hypertension were randomly assigned to two parallel treatment groups, one group (n = 11) received Ketanserin (40 mg/day) and the other one (n = 13) metoprolol (200 mg/day). After 3 months double-blind treatment, all patients received Ketanserin, on an open basis for one year alone or combined to metoprolol if Ketanserin failed to normalize DBP. A significant antihypertensive effect was demonstrated after 3 months double-blind treatment, for Ketanserin and metoprolol, in both standing and supine position (p less than 0.01). Heart rate showed a clear decrease by metoprolol (p less than 0.01). In the one-year follow-up, patients were divided in: I (n = 7) patients on Ketanserin (previously treated with the same drug); II (n = 4) patients on Ketanserin plus metoprolol (previously treated with Ketanserin, in whom it failed to normalize DBP); and III (n = 13) patients on Ketanserin (previously treated with metoprolol). In group I the blood pressure lowering effect of Ketanserin remained constant after one-year follow-up. In group II, although the number of patients was insufficient, a trend in the decrease of parameters was observed. In group III, supine and standing DBP diminished from 92.5 +/- 8 and 92.5 +/- 7 during treatment with metoprolol to 83.6 +/- 9 and 79.8 +/- 8 mmHg respectively at 12 months, after treatment with Ketanserin (p less than 0.05); accordingly, the cumulative percentage of normalized DBP increased from 4/13 after metoprolol to 12/13 at the end of the trial. Ketanserin side effects were minimal. Taking into account the wide variety of contraindications or side effects with beta-blockers and diuretics, Ketanserin appears as a new and important alternative in the treatment of mild and moderate essential hypertension.