Plasma thymulin (active and total) levels; IGF-I and zinc concentrations were evaluated in 9 children and in 8 adults with GH-deficiency (GHD) before and after 3-6 months of recombinant-GH treatment. Before therapy, GH deficient children had lower plasma active thymulin levels (1.0 +/- 0.3 log-2), not due to a peripheral defect in zinc saturation since plasma zinc levels were within the normal range, and total thymulin levels (1.3 +/- 0.3 log-2) than in the age-matched control group. GH therapy significantly increased active thymulin (3rd month: 3.0 +/- 0.2 log-2, 6th month: 4.0 +/- 0.2 log-2), total thymulin (3rd month: 3.3 +/- 0.3 log-2, 6th month: 4.3 +/- 0.2 log-2) and IGF-I levels (3rd month: 283.3 +/- 7.2 micrograms/L, 6th month: 411.2 +/- 44.2 micrograms/L, vs basal: 144.3 +/- 11.5 micrograms/L); at the 6th month of therapy, thymulin levels (active and total) were comparable to those found in controls. A positive correlation existed between zinc and plasma IGF-I levels (r = 0.66, p < 0.05). In adults with GHD, plasma active (1.9 +/- 0.3 log-2) and total thymulin levels (3.9 +/- 0.1 log-2), significantly lower (p < 0.01 and 0.05, respectively) than in controls before treatment, increased after GH therapy (active thymulin, 3rd month: 3.0 +/- 0.2 log-2, 6th month: 4.4 +/- 0.3 log-2; total thymulin, 3rd month: 3.9 +/- 0.3 log-2, 6th month: 4.7 +/- 0.2 log-2), being at 6th month of therapy no more different from the values recorded in the age-matched control group. In conclusion, children and adults with GHD have a marked impairment of the thymic endocrine activity, which can be restored by six months of GH treatment. The effects of GH on thymic functions may be mediated by IGF-I, through the modulation of zinc turnover, suggesting the possible existence of an interplay among GH, zinc, IGF-I and thymulin both in children and adults with GHD.