Taking advantage of high prevalence of prolactinomas in Newfoundland families with variant multiple endocrine neoplasia Type I (MEN I), we studied the control of prolactin secretion by dopamine in family members with prolactinomas (n = 6), family members who have hyperparathyroidism but no prolactinomas (n = 6), as well as healthy members (n = 8) in unaffected sibships. Four unrelated patients with empty sella syndrome were also studied as sella size controls for the prolactinoma group. Dopamine (2 micrograms/kg/min) was less effective in reducing serum prolactin in the prolactinoma group than in the other three groups studied; serum prolactin also showed little rebound in prolactin comparable to controls. Family members with hyperparathyroidism but no prolactinoma (and to a lesser degree the empty sella syndrome group) showed much less post-infusion rebound than controls. We conclude that family members genetically predisposed to prolactinoma (and patients with empty sella syndrome) may exhibit subtle abnormalities in dopaminergic control of prolactin secretion.