The consequences of human GH (hGH) secretion on hypothalamic, pituitary, and testicular functions in adult male transgenic mice bearing the hGH gene were evaluated. Two experiments were conducted. In Exp I, transgenic and nontransgenic littermate mice were treated with saline or GnRH in saline (1 ng/g BW). Fifteen minutes after the above treatment, blood samples were obtained for hormone measurements. In Exp II, transgenic and nontransgenic littermate mice were bilaterally castrated, treated with peanut oil or testosterone propionate (TP; 1 microgram/g BW). Blood samples were obtained from half of the animals at 24 h and from the remaining mice 48 h after oil or TP injection. In transgenic mice expressing the hGH gene, plasma PRL levels were significantly lower (P less than 0.001), but circulating LH levels were higher (P less than 0.001) than those in their normal littermates. Administration of GnRH significantly increased (P less than 0.001) plasma LH levels in both groups of mice. However, relative to basal LH levels, the LH response to GnRH treatment was attenuated in transgenic mice. Basal as well as GnRH-stimulated levels of FSH and testosterone were similar in transgenic and nontransgenic littermate mice. In normal castrated mice, plasma LH levels were significantly suppressed (P less than 0.001) 24 h after a single injection of TP. However, the same treatment was ineffective in transgenic mice. The negative feedback effect of TP on plasma FSH levels was also attenuated in transgenic mice. Since it is known that hyperprolactinemia increases LH secretion in male mice, our results demonstrate that transgenic mice are hypoprolactinemic with regard to pituitary PRL secretion, yet due to the lactogenic function of hGH, these animals are physiologically hyperprolactinemic. Thus, the expression of the hGH gene results in a derangement of hypothalamic-pituitary function in adult male transgenic mice.