In recent clinical trials, aldosterone, a well-established hormone in blood pressure and electrolyte control, has been shown to be involved in the development of cardiovascular and renal injury. We hypothesize that aldosterone elicits its pathological actions, at least partly, through an upregulation of EGFR, a heterologous signal transducer that can lead to hypertrophy and fibrosis and whose expression has been show to be aldosterone-inducible. To attain more information about the molecular mechanism of the EGFR upregulation caused by aldosterone, we studied the interaction between ligand-bound MR and the EGFR promoter with a reporter gene assay. After finding that aldosterone-bound MR enhances EGFR expression via the EGFR promoter we created deletion constructs of the MR and the EGFR promoter and assayed their reporter gene activity, identifying the domains important for this phenomenon. The data obtained indicate that the DNA-binding domain of the MR and the base pairs ( 317) ( 164) of the EGFR promoter are crucial for aldosterone-induced upregulation of EGFR expression. Further experiments with MR immunoprecipitation followed by EGFR promoter specific PCR (chromatin immunoprecipitation assay) and EMSA confirmed our results. This could be a first step in identifying new therapeutical targets for prevention of renal and cardiovascular remodeling caused by aldosterone.