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Renal dopamine D(1)-like receptors (D(1)Rs) and angiotensin type 2 receptors (AT(2)Rs) are important natriuretic receptors counterbalancing angiotensin type 1 receptor-mediated tubular sodium reabsorption. Here we explore the mechanisms of D(1)R and AT(2)R interactions in natriuresis. In uninephrectomized, sodium-loaded Sprague-Dawley rats, direct renal interstitial infusion of the highly selective D(1)R agonist fenoldopam induced a natriuretic response that was abolished by the AT(2)R-specific antagonist PD-123319 or by microtubule polymerization inhibitor nocodazole but not by actin polymerization inhibitor cytochalasin D. By confocal microscopy and immunoelectron microscopy, fenoldopam translocated AT(2)Rs from intracellular sites to the apical plasma membranes of renal proximal tubule cells, and this translocation was abolished by nocodazole. Because D(1)R activation induces natriuresis via an adenylyl cyclase/cAMP signaling pathway, we explored whether this pathway is responsible for AT(2)R recruitment and AT(2)R-mediated natriuresis. Renal interstitial coinfusion of the adenylyl cyclase activator forskolin and 3-isobutly-1-methylxanthine induced natriuresis that was abolished either by PD-123319 or nocodazole but was unaffected by specific the D(1)R antagonist SCH-23390. Coadministration of forskolin and 3-isobutly-1-methylxanthine also translocated AT(2)Rs to the apical plasma membranes of renal proximal tubule cells; this translocation was abolished by nocodazole but was unaffected by SCH-23390. The results demonstrate that D(1)R-induced natriuresis requires AT(2)R recruitment to the apical plasma membranes of renal proximal tubule cells in a microtubule-dependent manner involving an adenylyl cyclase/cAMP signaling pathway. These studies provide novel insights regarding the mechanisms whereby renal D(1)Rs and AT(2)Rs act in concert to promote sodium excretion in vivo.