The acute response to various doses of human growth hormone (hGH) was determined in short patients with thalassaemia and compared to that in patients with classic growth hormone deficiency and Turner's syndrome. Nitrogen balance was analyzed using the stable isotope 15N. While patients with growth hormone deficiency responded with a marked nitrogen retention (+2.9 +/- 0.4 to +6.1 +/- 0.6 mg 15N/kg) to small doses of hGH (2 x 3 IU/m2), those with Turner's syndrome had a higher basal balance, but responded much less (+3.1 +/- 0.7 to +3.7 +/- 1.8 mg 15N/kg). They required a double dose of hGH (2 x 6 IU/m2) to achieve a significant retention (+4.1 +/- 1.0 to +7.1 +/- 0.4 mg 15N/kg). The thalassaemic patients responded still less than the patients with Turner's syndrome to 2 x 6 IU/m2 (+7.7 +/- 0.3 to +8.0 +/- 0.4 mg 15N/kg), and even hGH doses up to 2 x 12 IU/m2 had little effect, indicating a relative resistance to hGH. In conclusion, no or little effect is to be expected from long-term hGH treatment at low doses in thalassaemic patients. When it is decided to treat these patients, the dose should be about 4 times higher than a regular replacement dose in growth hormone deficiency.