A pharmacological approach was used to study the involvement of opioid peptides and dopamine in mediating the suckling-induced release of prolactin in the lactating ewe (10–20 days post partum). To promote reliable and predictable suckling activity lambs were fitted with elasticated masks to prevent sucking for 4.5 h. After a 1-hour control period of frequent blood sampling, ewes were treated (i.v. injections every 5 min) for a further 75 min with either saline vehicle, an opioid antagonist (naloxone; 4.17 mg/5 min), a dopamine antagonist (metoclopramide; 1.25 mg/5 min), a mixture of naloxone + metoclopramide or a dopamine agonist (apomorphine; 6.6 mg/5 min). Blood was withdrawn at 5-min intervals for determination of plasma prolactin and luteinizing hormone (LH) by radioimmunoassay. Plasma LH concentrations (<1 µg/1) were not significantly affected by any of the drug treatments and there was no evidence for an acute fall in LH associated with suckling- or TRH-induced increases in prolactin secretion. Naloxone significantly (p < 0.05) reduced the mean incremental change in prolactin concentration (ΔPRL) in response to suckling (+ 7 ± 18 µg/ml) compared with saline-infused controls (+79 ± 26 µg/ml), an effect which was completely reversed by combined treatment with naloxone and metoclopramide (+146 ± 56 µg/ml). Metoclopramide alone raised basal prolactin levels by 46% (p< 0.01) but did not affect ΔPRL in response to suckling (+115 ± 52 µg/ml). Neither naloxone, metoclopramide nor a combination of the two drugs affected the subsequent prolactin to TRH (10 µg). Apomorphine, however, completely abolished both the suckling- and TRH-induced release of prolactin. These data are consistent with the hypothesis that the suckling-induced release of prolactin in the ewe depends on a reduced activation of dopamine receptors on pituitary lactotrophs which may be the result of a transient inhibition of dopamine release by endogenous op