The secretion and release of prolactin from the anterior pituitary is under the tonic inhibitory control of endogenous dopamine produced in the central nervous system. Exogenous dopamine inhibits prolactin secretion by reaching the pituitary via the portal circulation, and the hypolactotropic effect of dopamine infusion has been documented in all age groups in humans. However, the maturation of lactotroph sensitivity to dopaminergic inhibition has not been studied. Therefore, we followed the changes in serum prolactin concentrations before, during, and after dopamine infusion in 19 sick preterm infants with a mean gestational age of 30.6+/-0.6 weeks during the first 3 days of life, and examined the relationship of the hypolactotropic effect of dopamine to gestational age and birth weight in this patient population. As expected, dopamine therapy resulted in a decrease in mean serum prolactin from 89.4+/-9.5 to 58.6+/-9.1 microg/l (p < 0.05) with a return of the serum prolactin concentration to the pretreatment level 2-6 h after discontinuation of drug administration (98.3+/-11.7 microg/l, p < 0.05). However, simple regression analysis of the individual data revealed that the magnitude of the dopamine-induced decrease in serum prolactin was significantly influenced by gestational age (p = 0.006) and birthweight (p = 0.037). Thus, our findings provide evidence for the maturation of pituitary lactotroph sensitivity to dopaminergic inhibition in the preterm human neonate.