After finding that dopamine can cause extensive changes in mammotroph ultrastructure within 2 min of administration, we further examined mammotrophs 20 and 40 min after dopamine injection when prolactin secretion had resumed. Dopamine (1,000 µg/kg) was injected into the right atrium of estradiol-primed male rats through indwelling cannulae. Rats were killed by decapitation 2, 20 and 40 min after dopamine treatment and their pituitaries were processed for electron microscopy. Within 2 min of administration, dopamine completely stopped prolactin release and significant changes in mammotroph ultrastructure were observed: (1) peripheral relocation of rough endoplasmic reticulum (RER) (‘dopamine barrier’); (2) fewer secretory granules in close proximity to the cell membrane; (3) fewer exocytoses, and (4) increased numbers of intracellular bodies’ associated with secretory granules (putative granule disposal system). 20 min following dopamine administration, when prolactin secretion had resumed, there appeared to be a breaking up of the ‘RER barrier’ in that more vesicular elements were seen and the amount of peripheral RER was reduced; more granules were adjacent to the cell membrane and exocytotic figures were more numerous. ‘Intracellular bodies’ decreased in number. By 40 min, mammotrophs appeared to resemble those of estradiol-primed controls with the RER stacked to one side of the cell and small numbers of ’intracellular bodies’. The correlation between ultrastructural changes in mammotrophs and prolactin release implies that the ‘RER barrier’ is part of a mechanism by which prolacti