Primary cultures of neonatal cardiac myocytes were used to determine the identity of second messengers that are involved in angiotensin II (ANG II) receptor-mediated effects on cardiac hypertrophy and the type of ANG II receptor that is involved in ANG II-induced cell growth. Treatment of myocytes with ANG II significantly increased the protein-to-DNA and the RNA-to-DNA ratios. ANG II accelerated rates of protein synthesis by 24.9%. Intracellular free calcium was transiently increased after ANG II exposure. The activity of protein kinase C in particulate fractions was transiently increased after exposure to ANG II but returned to control level. The activity of protein kinase C in the cytosol was significantly decreased at all times after exposure to ANG II. After ANG II treatment, the content of c-Fos mRNA was increased. The stimulatory effects of ANG II on these parameters were inhibited by the type 1 angiotensin II receptor (AT1) antagonist, losartan. These studies demonstrate that ANG II-induced hypertrophic growth is, at least in part, mediated through AT1 receptors.