Prolonged growth hormone deficiency (GHD) leads to marked cardiac dysfunction; however, whether reversal of this abnormality may be achieved after specific replacement therapy has not yet been completely clarified. Fourteen patients with childhood-onset GHD (nine men and five women, mean age 27+/-4 years) and 12 normal control subjects underwent equilibrium radionuclide angiography under control conditions at rest. Patients with GHD were also studied 6 months after recombinant human (rh) GH treatment (0.05 IU/kg per day). Normal control subjects and patients with GHD did not differ with respect to age, gender and heart rate. In contrast, left ventricular ejection fraction (53%+/-9% vs 66%+/-6%, P <0.001), stroke volume index (41+/-11 vs 51+/-8 ml/m2, P <0.01) and cardiac index (2.8+/-0.6 vs 3.+/-0.5 l/min/m2, P <0.001) were significantly lower in GHD patients than in normal control subjects. None of the GHD patients showed adverse or side-effects during rhGH therapy; thus none required a reduction in GH dose during the treatment period. Heart rate and arterial blood pressure were not significantly modified by rhGH treatment. After 6 months of rhGH therapy a significant improvement in left ventricular ejection fraction (from 53%+/-9% to 59%+/-9%, P <0.01), stroke volume index (from 41+/-11 to 47+/-13 ml/m2, P <0.05) and cardiac index (from 2.8+/-0.6 to 3.3+/-0.8 l/min/m2, P <0.01) was observed in GHD patients. In conclusion, prolonged lack of GH leads to impaired left ventricular function at rest. Reversal of this abnormality may be observed after 6 months of specific replacement therapy in patients with childhood-onset GHD.