The ability of GH to regulate its own receptor in adipocytes of hormone-substituted hypophysectomized rats was studied. Male rats (130-150 g) were hypophysectomized and substituted with T4 and cortisone. A fixed dose of GH (bovine GH, human GH, or ovine GH), was administered for 5-6 days in three different ways: 1) two injections/day, 2) four injections/day, or 3) by osmotic minipumps. GH binding was measured in cell aliquots using [125I]human GH. In unsubstituted hypophysectomized animals, GH binding was decreased and was approximately 25% of the binding observed in adipocytes of normal rats. With T4 and cortisone replacement, GH binding was partially restored. When GH was administered in four daily injections or via osmotic minipumps, a further increase in GH binding was observed. This increase was observed if the animals were killed up to 6 h but not 12 h after the last GH injection. GH given in two daily injections had no effect on GH binding even when studied at different time periods after the last GH injection. The GH receptor induced by frequent or continuous administration of GH was mainly somatogenic, since an excess of unlabeled ovine PRL inhibited GH binding only to a minor extent. There was no difference in accumulated body weight gain between the GH-treated groups during the treatment period. The results show that GH regulates its own receptor in adipocytes and that the mode of administration of the hormone is of importance for this effect of GH.