Patients with mitral valve prolapse syndrome (MVPS), vasoregulatory asthenia, and poor postural adjustment often have orthostatic intolerance characterized by tachycardia and a narrow pulse pressure on standing. Autonomic dysfunction is thought to play an important role. Increased alpha-adrenergic activity has been shown in MVPS patients with orthostatic intolerance. We measured hemodynamic and neuroendocrine responses to long-term oral clonidine therapy in eight women, aged 36 +/- 1.8 years (27 to 44 years). None had responded favorably to beta-blockers. Heart rate, blood pressure, oxygen consumption, cardiac output, and plasma norepinephrine levels were measured in both supine and standing positions, before and after one to four weeks of clonidine (0.3 to 0.4 mg daily). Clonidine reduced standing plasma norepinephrine levels, total peripheral resistance, and diastolic blood pressure; a smaller decrease in cardiac output on standing was noted. Plasma volumes increased 12 percent. Mild reductions in plasma catecholamines and total peripheral resistance are associated with fewer, not more, orthostatic symptoms in this group of patients. "Placebo" or mild sedative effects may explain part of the response to clonidine, but the hemodynamic and neuroendocrine data suggest that decreased alpha-adrenergic hyperactivity may also be important.