We assessed the change of homocysteine (Hcy), insulin-like growth factor one (IGF-I) and oestrogen (E2) levels in patients with erectile dysfunction (ED) associated with chronic hepatitis C virus (HCV) infection. Eighty-five male patients with chronic HCV and/or ED were enrolled in this study. Seventy-five men were assigned to three equal groups (n = 25/each); Group A: patients who had chronic HCV and ED. Group B: patients who had chronic HCV and had no ED complaint. Group C: patients who had ED with no chronic HCV. In addition to 10 control patients with no ED or chronic HCV (Group D). All patients were subjected to: detailed medical and sexual history, complete physical examination, laboratory assessment including measurement of serum Hcy, IGF-1 and E2. The means of international index of erectile function scores were 8 and 16 in groups A and C respectively. There were significant differences in Hcy, IGF-I and E2 among study groups (p < 0.05 for each). There were significant differences in Hcy between patients with Child B and Child C. A strong association between severity of ED and chronic HCV was demonstrated. There was statistically significant increase of Hcy and E2 levels and reduction in IGF-I level in patients with ED associated with chronic HCV infection.