Oxandrolone (Ox) and testosterone (T) are used as growth-promoting agents in the therapy of boys with constitutional delay of growth and adolescence. Although the mechanism of action of these androgens is not known, it is recognized that T enhances GH release during GH stimulation tests. We studied the effects of T and Ox on the mean concentration of GH, the pattern of GH secretion, and somatomedin-C (SmC) concentrations in boys with short stature and/or delayed sexual developmentto determine whether their growth-promoting effects might be mediated through endogenous GH release. Ten boys received Ox (0.1 mg/kg-day, orally) for 65 ± 5 days (mean ± SD), and fiveboys received T propionate (7.5 mg, im, for 7 days), followed by T enanthate (100 mg, im, monthly for 3 months). Serum GH was measured in samples obtained at 20- min intervals for 24 h before and 65± 5 days (mean ± SD) after the initiation of therapy. SmC levels were measured twice during the same 24-h period before and 65 ± 5 days (mean ± SD) after initiation of therapy. In the boys treated with T, there were significant increases in the mean concentration of GH (meanincrease, 4.3-fold; range, 2-12), in the number of GH pulses 10 ng/ml or greater [1.6 ± 2.0 vs. 4.8 ± 1.5/24 h (mean ± SD)], and in the SmC levels [0.82 ± 0.46 vs. 2.3 ± 0.4 n/m/ (mean ± SD)]. There were, however, no significant changes in the boys treated withOx. Both Ox and T significantly improved the growth rates; however, T increased the growth rate by0.95 ± 0.24 (mean ± SD) cm/months, and Ox increased the growth rate by 0.24 ± 0.26(mean ± SD) cm/month. These results indicate that T, but not Ox, at the doses tested increases GH secretion in boys withshort stature and/or delayed sexual development. This increase in GH secretion may contribute to the increased growth rate in males at puberty.