Widespread use of the Beagle dog for long-term toxicity studies of hormonal contraceptives including progestagens-only, have resulted in proliferative mammary gland changes. The "tumorigenic potency" of progestagens in the dog has been related to an interaction between progestagens and prolactin (PRL) or growth hormone (GH) secretion. We therefore investigated the effect of a hydroxy-progesterone type progestagen (cyproterone acetate, CPA) and a nortestosterone type progestagen (norethisterone oenanthate) on serum PRL and GH concentrations. Furthermore, the effect of CPA on the GH and PRL producing cells of the anterior pituitary was examined immunoenzyme-cytochemically. Regardless of the structural type of the progestagens tested and the presence of mammary gland enlargement, serum PRL and GH levels were not clearly enhanced. Similarly, the immunoenzyme-cytochemical investigations of the anterior pituitary gland after treatment with CPA showed the PRL cells to be unaffected. In contrast, the GH producing cells exhibited obvious morphological signs of increased secretory activity even before related changes in serum GH concentrations became detectable.