We investigated the involvement of arginine vasopressin (AVP) V₁- and V₂-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10-14-fold. Pretreatment with the selective V₁-receptor antagonists [1-(p-t-butyl-β-mercapto-β,β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine] vasopressin or [1-(β,-mercapto-β,β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vasopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V₂-receptor antagonist [1-(β-mercapto-β, β-cyclopentamethylene propionic acid)-2-D-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V₁-receptor antagonist [1-p-t-butyl-β-mercapto-β,β-cyclopentamethylene propionic acid)-2-O-methyl)tyrosine-8-D-arginine]vasopressin and the V₂-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V₁-antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stressinduced secretion of PRL, and that the AVP receptor involved is primarily of the V₁-type or similar to this.