The PRL inhibitory effect of dopamine (DA) in human in vivo studies has been previously demonstrated with DA infusions at rates generally exceeding 2 micrograms/kg . min. We report here the effects of a DA infusion administered at a rate of 0.02 microgram/kg . min for 180 min to 10 normal subjects and 25 hyperprolactinemic patients with pituitary tumors (13 microprolactinomas, 8 macroprolactinomas, and 4 expanding nonsecreting pituitary adenomas). Serum free DA concentrations during the 3-h DA infusion reached an average of 0.8 +/- 0.1 ng/ml (about an 8- to 10-fold rise from basal levels). DA produced a significant (P less than ) 0.001) decline in plasma PRL levels in both normal subjects and hyperprolactinemic patients. There was a negative linear correlation between the serum DA concentrations and the percent PRL variation from basal levels (r = -0.58; P less than 0.001). The comparison of RPL responses between the different groups revealed that the mean percent overall PRL inhibition was significantly lower in patients with microprolactinomas than in normal subjects (P less than 0.02). On the other hand, PRL inhibition was greater in patients with nonsecreting adenomas than in either patients with microprolactinomas or those with macroprolactinomas (P less than 0.001). From 90-180 min, PRL suppression was also greater in patients with nonsecreting adenomas than in normal controls (P less than 0.05). The present study shows that 1) slight elevations of plasma DA are sufficient to inhibit PRL secretion, suggesting that DA acts as major physiological PRL-inhibiting factor, 2) there is a relative PRL resistance to DA inhibition in microprolactinoma patients; and 3) PRL is hyperresponsive to DA in expanding nonsecreting pituitary tumors.