Nitric oxide (NO), the key mediator synthesized by different NO synthase isoenzymes, plays an important role in endothelial function. It was recently shown that hyperhomocysteinemia is an important regulator of NO synthase. We investigated the role of homocysteine (Hcys) in erectile dysfunction (ED), which is associated with the defect in NO generation. Thirty-one nondiabetic patients and 33 control cases were evaluated. Patients with diabetes, coronary artery disease, vitamin B(12), or folate deficiency were excluded in the study. The International Index of Erectile Function questionnaire was used to gauge identified erectile quality. Fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, vitamin B(12), folic acid, and Hcys levels of patients were measured. Penile color Dupplex ultrasound was used to detect vascular abnormalities in nondiabetic patients with ED. Patients with ED were older than the control subjects (55.6 +/- 8.4 vs 44.5 +/- 4.7 years, respectively; P < .001). Patients with ED had higher fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, and Hcys levels. There was a significant negative correlation between mean Hcys level and mean International Index of Erectile Function domain score (P < .001). The penile color Doppler ultrasound findings showed that there was a negative significant correlation between mean Hcys level and the 1st, 5th, and 10th minute's peak-systolic velocity. Logistic regression analysis revealed that age and Hcys levels were the main determinants in ED. Hyperhomocysteinemia, known to be an important risk factor in endothelial dysfunction, seems to be an important determinant in ED. These data suggest that slightly elevated Hcys levels are significantly related with arterial and probably endothelial dysfunction in patients with ED.