Opposing effects of Angiotensin IV (Ang IV) have been reported in the rat kidney. Whereas it was found to induce renal vasodilation mediated by AT4 receptors in some studies (Coleman et al., 1998), renal AT1 receptor-mediated vasoconstriction was found in another study (Fitzgerald et al., 1999). There is convincing evidence that the AT4 receptor is the insulin-regulated aminopeptidase IRAP (Albiston et al., 2001). We investigated the effect of Ang IV on mean arterial pressure (MAP) and renal cortical blood flow (CBF) in wild type (WT), AT2 receptor and IRAP knock out mice as compared to Ang II, and AT4-16, a selective AT4 ligand. Moreover the pressor and renal responses to Angiotensin A (Ang A), a newly identified member of the angiotensin family, reported to have a similar affinity for the AT1 receptor as Angiotensin II (Ang II), but a higher affinity for the AT2 receptor (Jankowski et al., 2007) was investigated. MAP was recorded via a femoral artery catheter and CBF was recorded using a laser Doppler probe; cortical vascular resistance (CVR) was calculated as MAP divided by CBF. The basal values of MAP, CBF, and CVR in WT mice are 80.04  3.80 mmHg, 82.94  8.40 ml/min/100 g tissue, 0.97  0.11 mmHg.min/ml/100 g tissue, respectively. Ang IV, Ang A and Ang II were delivered as i.v. bolus injections via vascular catheters to the mice. In WT mice, all three Ang peptides dose–dependently increased MAP and CVR, and reduced CBF; moreover, these responses were antagonized by AT1 receptor blockade with candesartan. On the other hand, the responses towards Ang IV, Ang A, Ang II in AT2 (-/-), and IRAP (-/-) mice did not differ from those observed in WT mice. Hypotensive or vasodilator responses were not observed, even not following AT1 receptor blockade. The results provide evidence that Ang II, Ang IV and Ang A mediate pressor responses and reduce renal blood flow in mice through stimulation of AT1 receptors. The results do not provide evidence for a putative IRAP/AT4 receptor-mediated vasodilator effect.