Angiotensin IV (Ang IV) has been reported to induce renal vasodilation in rats via AT₄ receptors in some studies but renal vasoconstriction mediated by activation of AT₁ receptors in other studies. AT₄ receptor was characterized as the insulin-regulated aminopeptidase (IRAP), a membrane anchored zinc-dependent metalloproteinase. We investigated the effect of Ang IV and angiotensin II (Ang II) on mean arterial pressure (MAP) and renal cortical blood flow (CBF) in wild type (WT), AT_1a, AT_1b, AT₂ receptor and IRAP knockout mice. MAP was recorded via a femoral catheter and CBF was measured using a laser Doppler probe; cortical vascular resistance (CVR) was calculated as MAP divided by CBF. Baseline values of MAP, CBF and CVR in WT mice were 71.83.9 mmHg, 78.86.7 ml/min and 1.00.1 mmHg.min/ml, respectively. Baseline MAP, CBF and CVR were significantly lower in AT_1a (-/) as compared to WT animals. AT₂ (-/-) mice had a significantly higher baseline MAP, but similar CBF and CVR. Ang IV and Ang II dose–dependently increased MAP and CVR, and reduced CBF in WT mice; these responses were antagonized by AT₁ receptor blockade with candesartan. The pressor and renal vasoconstrictor responses to both peptides were almost completely abolished in AT_1a (-/-), but tended to be enhanced in AT₂ (-/-) mice. The responses in AT_1b (-/-) and IRAP (-/-) mice did not differ from those in WT mice. AT4–16 (100 nmol/kg) did not induce any effect in all types of mice. The results demonstrate that Ang IV and Ang II mediate pressor responses and reduce renal blood flow in mice through stimulation of AT_1a receptors, and suggest that the presence of AT₂ receptors may counteract these responses to some extent. The results do not provide evidence for a putative IRAP mediated vasodilator effect.