The epidermal growth factor receptor (EGFR) seems to be involved in the development of cardiovascular diseases. It can either be activated, by its ligands, or transactivated, by e.g. angiotensin II or aldosterone. Unfortunately, the consequences of EGFR activation in the cardiovascular system are not sufficiently understood. To evaluate the impact of the EGFR in the cardiovascular system, two mouse models with deletion of the receptor in vascular smooth muscle cells (VSMC) and cardiomyocytes (CM) were generated and analysed. In the heart the EGFR inhibits cardiac hypertrophy and is involved in the generation of the basal, vascular tone. In pathophysiological conditions the EGFR increases the impact of the renin-angiotensin-aldosteron system by i) partially mediating the vasoconstrictive response induced by angiotensin II and ii) by increasing the cardiovascular effects of inadequatly high aldosterone plasma levels. Additionally, it could be demonstrated in vitro that the effect of EGFR transactivation depends partially on the transactivating substance.