Both GH deficiency and excess are associated with cardiovascular disease. The mechanisms are unclear, but direct effects of GH in the vessel wall may be important. Previous reports suggest that GH enhances endothelium-dependent vasodilatation and alters large artery structure. Here we report a detailed assessment of large artery and microvascular structure and function in patients with contrasting GH levels. We studied six age-matched healthy control men, five men with acromegaly, and seven men with adult-onset GH deficiency before and at the end of 16 wk of GH replacement therapy. We measured arterial wall thickness by ultrasound of the common carotid artery; arterial stiffness by pulse wave analysis at the radial artery; microvascular structure by measurement of flow during maximal dilatation in the forearm and dermal circulation and counting dermal capillaries using video microscopy; and endothelial function in the forearm during brachial artery infusion of vasodilators (acetylcholine and sodium nitroprusside). Cardiac output was measured by Doppler ultrasound in GH-deficient patients and controls. GH-deficient patients tended to have increased arterial wall thickness and arterial stiffness, compared with controls. GH replacement reduced arterial stiffness (radial augmentation index 0.28 +/- 0.07 to 0.20 +/- 0.12, P = 0.02) and increased the number of dermal capillaries perfused (28.6 +/- 5.0 to 30.9 +/- 6.5 cm(-2), P = 0.03), but a reduction in arterial wall thickness was not statistically significant. With respect to maximum flow in forearm and dermis and endothelial function, GH-deficient patients were not different from controls, and GH therapy had no effect. Moreover, acromegalic patients were not different from controls in any vascular parameters studied. We conclude that the direct vascular effects of GH excess and deficiency in man are of modest magnitude and should not therefore be given the highest priority in considering the risks of cardiovascular events in patients with pituitary disease.