OBJECTIVE To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human penile erectile tissue. MATERIALS AND METHODS Penile fragments were removed from four young healthy organ donors (aged 17-28 years), and processed for immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm the expression of VEGF and Angs in erectile tissue. RESULTS VEGF and VEGFR1 expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a scattered distribution mostly in the perivascular SM layer, showing co-localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2 was not detected by immunohistochemical studies, but the use of the same antibody in molecular analysis confirmed Ang2 expression in human corpus cavernosum. CONCLUSIONS We show for the first time the co-localization of VEGF and Ang1 in the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be available for neoangiogenesis, if challenged. Studies of endothelial markers, growth factors and specific receptors are useful for understanding vascular organization and angiogenesis in normal human erectile tissue. This knowledge will be fundamental for developing newer therapeutic approaches to prevent or even cure erectile dysfunction.