We studied the effects of GH administration on myocardial structure and function in 20 patients with hypopituitarism (14 males and 6 females; mean +/- SE age, 47.2 +/- 2.6 yr; range, 31-59 yr) developed in adulthood because of pituitary or parapituitary tumors. All patients had GH deficiency (GHD), as assessed by a GH response of less than 4 micrograms/L to a standard insulin tolerance test (0.05 U kg, iv) and the combined pyridostigmine (120 mg, orally, at -60 min) plus GHRH (1 microgram/kg, iv, at 0 min) test. Patients received either placebo (n = 10) or GH substitution therapy (n = 10; 0.05 U/kg.day GH for 1 yr; 0.03 U/kg.day during the first month). M- and B-mode echocardiography and pulsed Doppler examination of transmitral flow were performed before treatment, 6 months and 1 yr after starting GH or placebo administration, and 15 days and 3 months after GH or placebo withdrawal. Twenty healthy subjects, matched for age, sex, body mass index, and physical activity, served as controls. Left ventricular dimensions, mass, and systolic function were normal in patients with adult-onset GHD; however, diastolic function, specifically E wave deceleration time, was altered. GH administration markedly increased left ventricular performance and reversed diastolic abnormalities at 6 and even more so at 12 months. On the other hand, a clear increase in left ventricular mass was seen after 12, but not after 6, months of GH administration (P < 0.01 vs. pretreatment values). In addition, although all changes induced by GH treatment disappeared within 3 months after GH withdrawal, at that time the increase in left ventricular mass was still detectable (P < 0.05 vs. pretreatment values). These data indicate that augmented left ventricular contractility is not strictly related to cardiac muscle growth, supporting the hypothesis that GH treatment increases the inotropic activity of myocardial fibers. In conclusion, GH treatment enhances cardiac function, increases cardiac mass, and reverses diastolic abnormalities in adults with hypopituitarism and GHD. However, long term studies are required to demonstrate that GH replacement therapy reduces cardiac death rate in these patients.