T he pathophysiological roles of the angiotensin II type 2 receptor (AT₂) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT₂ we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT₂ is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT₂ deletion were independent of activation of embryonic genes for cardiac hypertrophy. However, p70^S6k, one of the key factors in cardiac hypertrophy, was markedly and specifically reduced in the ventricles of Agtr2^–/Y mice. We propose that p70^S6k plays a major role in AT₂-mediated ventricular hypertrophy.This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org. J. Clin. Invest. 105:R25–R29 (2000).