There is evidence that some antihypertensive drugs, such as beta blockers, are effective in reducing intraocular pressure (IOP) and are commonly used in the medical treatment of glaucoma. The aim of this study was to evaluate the effects of the anti-serotonergic agent ketanserin, which has associated alpha 1-blocking properties, on IOP in normotensive and hypertensive eyes. The first part of the study was performed in six arterial hypertensive patients (mean +/- SD blood pressure 156/102 +/- 10/6 mmHg) with a pretreatment IOP in the normal range (15.7 +/- 1 mmHg). Both blood pressure and IOP were measured at baseline and at 1 hour intervals up to 3 hours following the oral administration of ketanserin 20 mg or placebo, given in a randomized manner. Three hours after ketanserin treatment, mean systolic and diastolic blood pressures dropped by 10/5 mmHg and mean IOP was reduced by 2.7 mmHg; after placebo, no change was observed in these variables. Thereafter, four normotensive patients with chronic open-angle glaucoma (IOP = 22.8 mmHg) were given 20 mg ketanserin orally. Three hours after administration, a 22% reduction in mean IOP occurred (-5.8 mmHg), with a concomitant reduction in mean systolic blood pressure of 13.0 mmHg. These results indicate that ketanserin treatment reduces IOP and systemic blood pressure. Further, long-term studies are needed in order to confirm the efficacy of ketanserin in the medical treatment of ocular hypertension.