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 (AT₁ and AT₂) are present in near equal proportions. Cotreatment with a 10-fold molar excess of AT₂ 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%). AT₂ antagonists enhanced Ang II stimulation of protein synthesis, as indexed by [³H]leucine incorporation, whereas an AT₁ antagonist blocked Ang II–induced incorporation. An AT₂ antagonist also prevented Ang II–induced protein degradation. In conclusion, Ang II–induced myocyte growth is tempered because of low AT₁ levels and an antigrowth effect of AT₂. These findings have potential clinical significance in that regression of hypertension-induced cardiac hypertrophy by AT₁ antagonists may be in part due to an unopposed antigrowth effect of Ang II mediated via AT₂.