The effects of long-acting calcium channel blockers on pressure overload-induced cardiac hypertrophy have been little studied in experimental animals and the underlying mechanisms are not fully understood. We previously reported that cardiomyocyte hypertrophy could be induced via phosphorylation of the epidermal growth factor receptor (EGFR). In this study, we investigated whether amlodipine attenuates cardiac hypertrophy by inhibiting EGFR phosphorylation. We found that amlodipine dose-dependently inhibited epinephrine-induced protein synthesis and EGFR phosphorylation in cultured neonatal rat cardiomyocytes. Our in vivo study revealed that amlodipine could ameliorate myocardial hypertrophy induced by transverse aortic constriction (TAC) in C57/B6 mice. One week after TAC, amlodipine treatment (3 mg/kg/day) significantly reduced the heart-to-body weight ratio (6.04 +/- 0.16 mg/g vs. 6.90 +/- 0.45 mg/g in untreated TAC mice, P < 0.01). These results indicate that amlodipine ameliorates cardiomyocyte hypertrophy via inhibition of EGFR phosphorylation.