Cardiac performance was investigated by radionuclide angiography in 11 patients with childhood-onset growth hormone (GH) deficiency and in 12 control subjects. Both at rest and during maximal physical exercise, systolic function was markedly depressed in GH-deficient patients. Ejection fraction rose from 66 +/- 6 to 76 +/- 7% during exercise in control subjects, whereas in GH-deficient patients it remained unchanged or even decreased (55 +/- 6 and 54 +/- 9% at rest and after exercise, respectively; P < 0.01 vs. controls). Cardiac index was significantly lower in GH-deficient patients than in controls, both at rest (2.7 +/- 0.6 vs. 3.7 +/- 0.5 l.min-1.m-2; P < 0.001) and during exercise (8 +/- 1.2 vs. 10 +/- 1.5 l.min-1.m-2; P < 0.01). Five GH-deficient patients were treated with recombinant human (rh) GH for 6 mo at a dose of 0.05 IU.kg-1.day-1. Cardiac index at rest improved from 2.8 +/- 0.6 to 3.3 +/- 0.8 l.min-1.m-2 (P < 0.01) after rhGH. Also, cardiac index response to exercise improved markedly and became similar to that of controls (7.5 +/- 1.2 and 10.1 +/- 1.1 l.min-1.m-2 before and after rhGH, respectively; P < 0.005). Exercise tolerance was impaired in GH-deficient patients and was restored by rhGH treatment. The data support the hypothesis that GH plays an important role in the maintenance of a normal cardiac performance in humans.