Subcellular responses of amphibian growth hormone (GH)-producing cells to in vivo administration of human pancreatic growth hormone-releasing factor (1-44) (hpGRF) were investigated. The volume density (Vv) of secretory granules (SG), rough endoplasmic reticulum (RER), and Golgi complex (GC) and the numerical density (Nv) of the granules were estimated by ultrastructural morphometry. Immunogold staining was applied to ultrathin sections using an antiserum to ovine GH to identify GH-producing cells. In vivo treatment with hpGRF significantly decreased the Vv of the SG and the Nv of medium SG after 6 hr. The peptide also stimulated development of the cellular biosynthetic machinery and increased the number of small SG 24 hr after stimulation. Four-day-stimulated GH cells did not recover control morphological appearances. These morphological results suggest that: (1) In vivo administered hpGRF stimulates GH cells in Rana perezi by inducing hormone release and enhances biosynthetic activity; (2) after four injections, the cellular response is more intense, indicating that GH cells remain hyperactive, probably because the exogenous hpGRF overcomes the endogenous inhibitory control of GH secretion.