Exercise hypotension has been documented in patients with hypertrophic cardiomyopathy (HCM). Some investigators reported that this is due to an inadequate increase of systemic vascular resistance during or after exercise. The aim of this study was to investigate the pathogenesis of limb vascular response abnormalities in patients with idiopathic HCM. Thirteen patients with HCM and 9 healthy controls were administered an endothelium-dependent dilator (acetylcholine), a direct smooth muscle dilator (nitroglycerin), an alpha-adrenergic stimulator (phenylephrine), and a beta-adrenergic stimulator (isoproterenol) by intra-arterial infusion. Peripheral vascular resistance was assessed by forearm plethysmography at rest and during each infusion to obtain the percentage change in vascular resistance. Isoproterenol, acetylcholine and nitroglycerin produced dose-related vasodilatation with no significant differences between HCM patients and healthy controls. The percentage increase in vascular resistance was significantly less in HCM patients than in healthy controls after phenylephrine infusions of 0.5 microg/min (155+/-38% vs 195+/-47%, mean+/-SD, p<0.05) and 1.0 microg/min (174+/-49% vs 238+/-65%, p<0.05). Vasoconstriction mediated by alpha-adrenergic receptors appeared to be impaired in the peripheral vasculature of patients with HCM.