The aim of this study was to assess the effects of ketanserin on insulin resistance in nondiabetic hypertensive patients. Eleven nonobese, nondiabetic mild to moderate hypertensives (6 males, 5 females, aged 39-59 years), after a 4 week run-in period on placebo, were treated with ketanserin 40 mg twice daily for 12 weeks. Blood pressure (BP) (by standard mercury sphygmomanometer) and insulin sensitivity (by the euglycemic hyperinsulinemic clamp technique) were evaluated at the end of the placebo period and at the end of the treatment period. Ketanserin produced a significant decrease in BP (from 160 +/- 13/100 +/- 4 mmHg to 146 +/- 10/89 +/- 5 mmHg p < 0.01). The amounts of exogenous glucose required to hold glucose levels constant during clamp were not changed by ketanserin as compared to placebo 34.5 +/- 3.5 g vs 33.8 +/- 3.1 g). The rate of glucose infusion required during the last 60 minutes of the clamp, used as an indicator of insulin sensitivity, was not different before and after treatment (5.52 +/- 0.41 mg/min/ kg vs 5.21 +/- 0.39mg/min/kg). These results suggest that in nonobese, nondiabetic hypertensive patients ketanserin monotherapy is effective in reducing BP values without affecting insulin sensitivity.