The growth hormone (GH)-insulin-like growth factor-1 axis has great relevance for the regulation of cardiac growth, structure, and function. GH deficiency may result in impaired cardiac performance, manifest by a reduction in left ventricular mass and ejection fraction, but data are inconsistent. GH therapy is recommended treatment in adult patients with GH deficiency, but in acromegaly, in which there is excess GH, the main cause of mortality is cardiovascular disease. The purposes of this study were to perform (1) a case-controlled study comparing cardiac morphology and function in 53 GH-deficient patients (34 men, mean age 38.1 +/- 15.2 years, 22 with childhood-onset GH deficiency) and 46 healthy controls (29 men, mean age 37.8 +/- 12.4 years) and (2) a longitudinal study to assess the effect of introducing GH therapy in 37 subjects for a mean period of 26 +/- 22 months. At study entry, all subjects underwent electrocardiography and 24-hour ambulatory electrocardiographic monitoring, systolic and diastolic blood pressure assessment, detailed echocardiography, and exercise tolerance tests. There were no significant differences in left ventricular mass, left ventricular dimensions, systolic or diastolic function indexes, or blood pressure at rest in patients compared with controls. Exercise duration was significantly shorter and peak heart rate during exercise (chronotropic response) lower in the GH-deficiency group than in controls (p <0.05). After GH treatment, there were no significant changes in echocardiographic parameters or blood pressure, but an improvement in exercise duration (p = 0.019) was found, particularly in the subgroup with childhood-onset GH deficiency (n = 16). In conclusion, patients with GH deficiency did not show cardiac structural or functional differences compared with healthy controls, with no significant changes after GH treatment. However, these patients exhibited improved exercise capacity, especially those with childhood-onset GH deficiency.