We compared the ability of angiotensin II (Ang II) to induce hypertrophy of neonatal rat ventricular myocytes with that of endothelin-1. Over 72 hours, Ang II (1 μmol/L) increased the ratio of protein to DNA by less than 10%, whereas endothelin-1 (100 nmol/L) produced a 28% increase. The growth effects of either agonist occurred independently of chronotropic actions. Radioligand binding studies showed that myocytes have nearly 300-fold more receptors for endothelin-1 than Ang II, and type 1 and type 2 Ang II receptor subtypes (AT 1 and AT 2 ) are present in near equal proportions. Cotreatment with a 10-fold molar excess of AT 2 antagonists (PD 123177 or CGP 42112) for 72 hours augmented the Ang II–induced increase in the protein-to-DNA ratio to levels nearly as high (23%) as those with endothelin-1 (28%). AT 2 antagonists enhanced Ang II stimulation of protein synthesis, as indexed by [ 3 H]leucine incorporation, whereas an AT 1 antagonist blocked Ang II–induced incorporation. An AT 2 antagonist also prevented Ang II–induced protein degradation. In conclusion, Ang II–induced myocyte growth is tempered because of low AT 1 levels and an antigrowth effect of AT 2 . These findings have potential clinical significance in that regression of hypertension-induced cardiac hypertrophy by AT 1 antagonists may be in part due to an unopposed antigrowth effect of Ang II mediated via AT 2 .