In order to investigate the influence of dopamine (DA) in modulating prolactin (PRL) response to vasoactive intestinal polypeptide (VIP), VIP (75 µg i.v. over 12 min) was administered to normal women and patients with microprolactinomas during saline or DA (0.06 µg/kg BW/min) infusion. In 8 normal women VIP caused PRL to rise from 7.9 ± 0.8 (mean±SE)to 33.4+ 17.1 ng/ml(p< 0.01), the peak occurring at 15 min, while it did not elicit any significant modification in serum PRL levels in 18 patients with microprolactinomas. DA infusion lowered serum PRL by 67 and 58.2% at 120 min in normal women and in patients with microprolactinomas, respectively, and abolished VIP-induced PRL response in normal women without influencing PRL response in patients with microprolactinomas. PRL responsiveness to VIP was not restored by dopaminergic disinhibition (domperidone 10 mg i.v.) in 4 patients tested. Two previously unresponsive patients showed a VIP-induced PRL increase, superimposable on that recorded in normal women, after successful selective adenomectomy. These data suggest that DA, although able to suppress VIP-induced PRL response in normals, does not play any major role in causing unresponsiveness to VIP in prolactinomas. The lack of PRL responsiveness to VIP might be intrinsic to the adenoma or due to alterations of PRL secretion regulatory mechanisms other than DA secondary to the presence of the tumor, or to a depletion of the readily releasable pool of