The present study was designed to characterize the time and dose relationships of the response of tuberoinfundibular dopaminergic (TIDA) neurons in the rat to systemically administered prolactin (PRL). The activity of TIDA neurons was estimated by measuring the rate of dopamine (DA) synthesis in the median eminence (DOPA accumulation following the administration of a decarboxylase inhibitor). Rats were pretreated with bromocriptine, a dopaminergic agonist, so as to inhibit the release of endogenous PRL from the anterior pituitary, and thereby reduce the activity of TIDA neurons to a ‘basal’ level from which it could be increased subsequently by exogenously administered PRL. In control animals an intraperitoneal injection of ovine PRL (oPRL) increased DOPA accumulation at 16 h, but not before, whereas in bromocriptine-pretreated animals an intraperitoneal injection of oPRL increased DOPA accumulation after 4 h (‘tonic’ component) and caused a further increase after 16 h (‘induction’ component). Continuous intravenous infusions of oPRL into bromocriptine-pretreated rats increased DOPA accumulation in the median eminence by 4 h, and when infused into control rats oPRL reduced serum concentrations of endogenous rat PRL (rPRL) by 2 and 4 h. Continuous intravenous infusions of rPRLincreased DOPA accumulation in the median eminence after 2 h; this effect exhibited a very steep dose-response relationship (possibly an ‘all-or-none’ response). TIDA neurons were very sensitive to changes in circulating concentrations of PRL; their activity was increased if serum PRL concentrations were merely doubled by infusing a low concentration of rPRL for 4 h. Three daily injections of haloperidol elevated circulating rPRL concentrations and increased the rate of DOPA accumulation in the median eminence. These effects were blocked by an injection of bromocriptine 4 h prior to sacrifice. In animals with ‘induced’ TIDA neurons (i.e., treated for 3 days with haloperidol and 4 h with bromocriptine), a 2-hour intravenous infusion of rPRL increased the rate of DOPA accumulation in the median eminence; the time of onset and dose of rPRL needed to trigger this effect in ‘induced’ TIDA neurons were not different from those in ‘control’ neurons. On the other hand, the magnitude of the increase in DOPA accumulation in response to intravenous infusions of rPRL was markedly increased in the ‘induced’ TIDA neurons. Thus, TIDA neurons that have been ‘induced’ by chronically elevated circulating concentrations of PRL exhibit a greater response to the acute administration of PRL. These results suggest that the magnitude of the activation of TIDA neurons by acute changes in circulating PRL concentrations (‘tonic’ component) is determined by the preceding history of circulating concen