Because dopamine influences arginine vasopressin (AVP) release, the present studies were designed to ascertain the dopamine receptor subtype that potentiates angiotensin II-induced AVP secretion in cultured hypothalamo-neurohypophysial explants. Dopamine (a nonselective D₁/D₂ agonist), apomorphine (a D₂  D₁ agonist), and SKF-38393 (a selective D₁ agonist) dose dependently increased AVP secretion. Maximal AVP release was observed with 5 µM dopamine, 307 ± 66% · explant¹ · h¹, 1 µM SKF-38393, 369 ± 41% · explant¹ · h¹, and 0.1 µM apomorphine, 374 ± 67% · explant¹ · h¹. Selective D₁ antagonism with 1 µM SCH-23390 blocked AVP secretion to values no different from basal. Domperidone (D₂ antagonist), phenoxybenzamine (nonselective adrenergic antagonist), and prazosin (₁-antagonist) failed to prevent release. D₁ antagonism also prevented AVP secretion to 1 µM angiotensin II [angiotensin II, 422 ± 87% · explant¹ · h¹ vs. angiotensin II plus SCH-23390, 169 ± 28% · explant¹ · h¹ (P < 0.05)], but D₂ and ₁-adrenergic blockade did not. In contrast, AT₁ receptor inhibition with 0.5 µM losartan blocked angiotensin II- but not dopamine-induced AVP release. AT₂ antagonism had no effect. Although subthreshold doses of the agonists did not increase AVP secretion (0.05 µM dopamine, 133 ± 44% · explant¹ · h¹; 0.01 µM SKF-38393, 116 ± 26% · explant¹ · h¹;and 0.001 µM angiotensin II, 104 ± 29% · explant¹ · h¹ ), the combination of dopamine and angiotensin II provoked a significant rise in AVP [420 ± 83% · explant¹ · h¹ (P < 0.01)]. Similar results were observed with SKF-38393 and angiotensin II, and the AVP response was blocked to basal levels by either D₁ or AT₁ antagonism. These findings support a role for D₁ receptor activation to increase AVP release and mediate angiotensin II-induced AVP release within the hypothalamo-neurohypophysial system. The data also suggest that the combined subthreshold stimulation of receptors that use distinct intracellular pathways can prompt substantial AVP release.