The effects of very high doses of human growth hormone (hGH), pituitary derived or recombinant methionyl-hGH, on the morphology of reproductive organs and on some hormones in the male dog are described. The studies were part of a toxicological documentation of hGH. A total of 18 male dogs aged 7.5-20.5 months, from four studies were treated subcutaneously with hGH for 20-28 days at dose levels of 3, 10 or 25 IU kg-1 day-1 or 1 IU kg-1 three times weekly. Plasma levels of luteinizing hormone (LH), testosterone and prolactin were determined in one study. Organ weighing, macroscopic and histopathologic examinations of male reproductive organs at the end of the treatment period were included in all studies. Treatment with 25 IU kg-1 day-1 resulted in reduction of testis and prostate weights, degeneration of germ cells and epithelial atrophy in the testis, degenerative changes in epididymis and reduced height of the prostatic epithelium. Similar, although less severe morphological changes were observed after treatment with 10 IU kg-1 day-1. Treatment with 25 IU kg-1 day-1 also caused a marked reduction of plasma prolactin, LH and testosterone levels. These results suggest that repeated administration of very high doses of hGH interferes with the hormonal regulation of the testis in the dog.