Growth hormone (GH) hypersecretion is associated with an increased incidence of hypertension and cardiac hypertrophy, resulting in excess cardiovascular morbidity and mortality. Abnormalities in the renin-angiotensin-aldosterone (RAA) system have been reported in acromegaly and in normal adults treated with recombinant human GH. The RAA system was investigated in prepubertal children with idiopathic short stature during treatment with recombinant human GH in doses up to 40 IU/m2/week. In addition, left ventricular size and function were assessed by serial echocardiography over an initial 12-month period. Modest and transient increases in blood pressure and body weight were observed during the first 7 days of GH treatment, but this was not accompanied by activation of the RAA system. Echocardiographic parameters of left ventricular size and function remained within the normal range for age and body size. Short-term GH treatment of idiopathic short stature was thus not associated with an increase in risk factors known to be associated with later cardiovascular morbidity. Longer follow-up studies will be required to confirm the safety of high-dose GH in this respect.