To elucidate the effect of a long-term antihypertensive therapy on blood pressure (BP) response to isometric handgrip exercise (IHG) in patients with essential hypertension (EHT, n = 16), IHG was carried out at 30% maximal voluntary contraction of right hand for 3 min before therapy and after a long-term antihypertensive therapy. BP responsiveness to IHG was estimated by the difference between values obtained at rest and at 3 min during IHG (change of systolic BP = DeltaSBP, change of diastolic BP = DeltaDBP. Both DeltaSBP and DeltaDBP before therapy were markedly greater in EHT (DeltaSBP = 64 plus minus 18 mm Hg, DeltaDBP = 33 plus minus 9 mm Hg) than in age-mathced normotensive controls (NT, n = 8, 29 plus minus 4 mm Hg, 18 plus minus 4 mm Hg). By antihypertensive therapy, SBP and DBP in EHT were decreased from 152 plus minus 22 mm Hg to 136 plus minus 14 mm Hg and from 90 plus minus 18 mm Hg to 83 plus minus 10 mm Hg, respectively, but both SBP and DBP in EHT after antihypertensive therapy were still greater than those in NT. Both DeltaSBP and DeltaDBP in EHT after a long-term antihypertensive therapy were significantly smaller than those in EHT before therapy but were still significantly larger than those in NT. These results demonstrate that a long-term antihypertensive therapy reduces the exaggerated BP response to IHG in EHT.