The purpose of this double blind, cross-over, randomized study was to assess the antihypertensive efficacy and tolerability of ketanserin given at two different doses (i.e. 20 or 40 mg b.i.d.) in a group of patients with essential hypertension aged over 60 years. In addition, we evaluated the effect of ketanserin on some indexes of the sympathetic nervous system activity and the renin-angiotensin-aldosterone system, as well as the pharmacokinetic characteristics of the drug after acute administration per os and during chronic treatment. Twelve hypertensive patients, 6 males and 6 females gave their informed consent to the study. Each patient underwent a non invasive blood pressure monitoring after a wash out period with placebo, after 5 weeks of treatment with ketanserin (20 or 40 mg b.i.d.), after a second wash out period with placebo, and after a second period of treatment (5 weeks) with ketanserin (40 or 20 mg b.i.d.). In addition, we evaluated ketanserin plasma levels during acute and chronic administration. During treatment with ketanserin 20 mg b.i.d. systolic and diastolic blood pressure showed a small, statistically not significant reduction. The higher dose (40 mg b.i.d.) reduced systolic and diastolic blood pressure. Three hours after administration of 40 mg of the drug, ketanserin plasma levels were higher than after administration of 20 mg; this difference disappeared after 24 hours. A statistically significant relationship between mean blood pressure reduction during chronic treatment and ketanserin plasma levels was detected. No adverse effects were detected. In conclusion, ketanserin seems to be well tolerated and useful in antihypertensive therapy in elderly patients, particularly at the dose of 40 mg b.i.d.