A stimulatory effect on prolactin secretion had been describe after acute and systemic administration of met-enkephalin, but the effects of this opioid after chronic administration has not been reported, and the response of mammotroph cells is not clear. As a complement to previous studies, a morphometric analysis (light and electron microscopy) was carried out on prolactin cells from female rats treated chronically with met-enkephalin. Clear features of cellular hyperactivity appeared after chronic and systemic administration of the opioid, and these persisted for two weeks. The changes consisted in increases of cellular, cytoplasmic and nuclear areas, volume and surface densities of the Golgi complex and rough endoplasmic reticulum, as well as the numbers of exocytotic figures. These morphological alterations were paralleled by an increase in serum prolactin levels as detected by RIA. It is concluded that the increase in the synthesis and secretory activity of prolactin cells following chronic and systemic administration of met-enkephalin is very similar to those observed after acute and intraventricular administration.