Insulin‐like growth factor (IGF)‐II is known to induce hypertrophy of isolated adult rat ventricular cardiomyocytes cultured in the absence of serum. However, it is not known how the growth factor exerts this hypertrophic effect. We show here that IGF‐II induces hypertrophy of the cultured cardiomyocytes via two alternative pathways: (1) an IGF‐I receptor‐dependent pathway, or (2) a lysosome‐dependent pathway when the IGF‐I receptor‐dependent pathway is blocked.