The serotonin (S2) antagonist, ketanserin was given to 16 patients with essential hypertension on a single-blind basis. Ten patients were treated for 3 years with ketanserin 40-80 mg daily on a once or twice daily regimen. In this group supine blood pressure fell from 164 +/- 4/101 +/- 2 mmHg on placebo to 152 +/- 5/91 +/- 3 mmHg (NS/P less than 0.01) after 3 years of therapy. During treatment, total serum cholesterol remained essentially unchanged while serum triglycerides were significantly reduced. No side-effects were seen except for dry mouth or slight nasal congestion reported by two patients. In six patients regional haemodynamics were assessed by forearm plethysmography. After 3 months of ketanserin, resting vascular resistance was significantly reduced from 58.3 +/- 12 units on single-blind placebo to 47.0 +/- 12 units (P less than 0.005) on single-blind ketanserin, 40 mg twice daily. We conclude that ketanserin is an effective antihypertensive agent during long-term therapy with some beneficial effects on serum lipids. The antihypertensive effect seems to be mediated chiefly by a decrease in vascular resistance.