The aim of this work is to study the presence of endothelial nitric oxide synthase in the cavernous tissue of the penis by immuno-histochemical methods in patients with organic failure of different aetiologies. The study included 20 impotent men presented to Kasr El-Aini Andrology Clinic. For all patients, the following was done : history taking, general examination, examination of genitalia, ICI (papaverine + phentolamine) test. Those who showed negative response to papaverine + phentolamine test underwent duplex and rig scan. Those patients who were indicated for the penile prosthesis implantation, an open biopsy was taken from the cavernous tissue of the mid shaft of the penis. These biopsies were subjected to fixation, dehydration, clearing and paraffin embedding. Sections were stained by the following histological and histochemical techniques: hematoxylin and eosin stain (for general architecture) and the other histologic section was used for detection of eNOS in cavernous tissue by immuno-histochemical staining monoclonal antibody (NCL-NOS3) which is the good sensitive marker for detection human (eNOS) in endothelial cells. It was found that 14 patients (70%) had veno-occlusive erectile dysfunction, while 4 patients (20%) has mixed vasculogenic erectile dysfunction, and two patients (10%) has arteriogenic erectile dysfunction. Regarding the risk factors, it was found that 11 patients (55%) were smokers and 10 patients (50%) were diabetics and 9 patients (45%) were hypertensives. As regards aging, we found that there was a statistical significant difference on comparing a two age groups (above > 50), below < 50 year old as regards the presence of eNOS. Regarding the presence or absence of endothelial nitric oxide synthase in the cavernous tissue in patient with erectile dysfunction and the presence of one of the risk factors (smoking, diabetes mellitus, and hypertension) there was no statistical significant difference between the presence of eNOS and the risk factors when exists alone. However, the presence of two or more risk factors as (smoking with hypertension) smoking with diabetes mellitus or (Hypertension with DM) smoking with diabetes mellitus and hypertension, there was a statistical significant difference between the presence of two or more risk factor and the presence of eNOS in cavernous tissue in patient with erectile dysfunction. Accordingly, we concluded from our study that, these risk factors may affect the presence of endothelial nitric oxide synthase which has an important role in normal erection. Moreover, the presence of more than one risk factor can significantly disturb nitric oxide mediated erectile mechanisms and caused impotence.