Eight patients with idiopathic hypopituitarism were studied to evaluate changes in hypothalamic-pituitary-thyroid function during the course of their therapy with hGH. Before treatment, 5 patients were in an euthyroid state with normal serum thyroxine (T4) levels and normal TSH response to TSH-releasing hormone (TRH) (group I), while 3 patients was associated with hypothalamic hypothyroidism (group II). Overall observation period was 6–14 months. Following 1–2 months of hGH therapy, serum T4-I concentrations decreased below the initial level both in group I and II (84 ± 23% and 60 ± 20% of the initial value, respectively, P < 0.05). However, patients of group I showed a prompt rise in serum triiodothyronine (T3) level, resulting in marked elevation of T3/T4 ratio and acceleration of growth, whereas in group II serum T3 remained unchanged at the previous level without promotion of growth rate (180 ± 40% vs. 105 ± 13%, P < 0.001). After L-T4 replacement for the latter, gradual increase in serum T3 with concomitant decrease in serum T4 ensued and their growth rate was apparently accelerated. A statistically significant correlation was noted between growth rate and serum T3 levels, but not serum T4 concentrations (r = 0.859, P < 0.01). In the course of hGH treatment, TSH responses to TRH showed substantial increase in the peak value (1.5–4 times) in all of group I, while there was no remarkable change in the exaggerated and delayed TSH responses in group II, which were completely suppressed after L-T4 replacement. These results suggest that in addition to other previously demonstrated effects of GH on the hypothalamic-pituitary-thyroid axis such as TSH inhibition, GH changes peripheral T4 metabolism, in which conversion of T4 to T3 may probably be accelerated, and the hypothalamic TRH release appears to play an important role in adaptation to this situation.