The expression of connexins in renal arterioles is believed to have profound impact on regulation of arteriolar tonus and renal blood flow. Connexin 40 (Cx40), which is primarily expressed in the endothelial cells of the renal afferent arterioles, has been shown to play a significant role in the regulation of renin secretion. Also, connexins are believed to be involved in the transmission of the calcium signal initiating the TGF response and connexins may therefore be involved in renal blood flow autoregulation. We wished to examine the renal autoregulatory response by measuring changes in afferent arteriolar diameter in kidneys from Cx40 knockout (KO) mice in response to a step increase in perfusion pressure. We used the isolated blood perfused juxtamedullary nephron preparation to visualize afferent arterioles. As previously reported Cx40 KO mice had a higher arterial blood pressure than age-matched litter- mate controls. Also, the plasma renin concentration was significantly higher in the Cx40 KO mice compared to wild-type mice. The change in afferent diameter in response to step increases in renal perfusion pressure was impaired in Cx40 KO mice compared to the wild- type littermates. These results suggest that Cx40 play a role in the autoregulation of renal blood flow.