The direct effect of short-term bromocriptine administration on human prolactin cell adenomas in vitro was studied by light and electron microscopy and correlated with the effect on hormone release. The light microscopic and, for the first time, ultrastructural characteristics of adenomatous prolactin cells in control and treated cultures were analyzed morphometrically and the changes induced by bromocriptine were quantified. Following 72 h treatment which lowered levels of prolactin release, there was a marked reduction in cell size, cytoplasmic volume and cytoplasmic volume densities of endoplasmic reticulum and Golgi apparatus. In contrast, the percentage of cytoplasm occupied by lysosomes increased. There was no consistent change in number and diameter of secretory granules. These findings indicate that prolactin cell involution is a direct effect of bromocriptine and suggest that reduction in endoplasmic reticulum and Golgi complex is largely responsible for the decreased cell size. Lysosomal degradation of cytoplasmic components may play a role in this process.