Our present study was to determine the collagen subtype pattern in the greater saphenous vein of the lower limb, obtained from 21 normal (macroscopically and ultrastructurally non-varicose vein segments from non-varicose subjects) and 37 varicose subjects, and to compare affected (macroscopically and ultrastructurally varicose segments from varicose veins) vs. non-affected (macroscopically and ultrastructurally non-varicose segments from varicose veins) segments (16). After elastase pretreatment and partial pepsin digestion, types I, III & V collagens (CI, CIII, CV) were extracted selectively by differential salt precipitation and measured quantitatively in samples obtained from normal and varicose saphenous veins-either affected or unaffected segments. Significant elevations of water (p < 0.05) and collagen type I [CI] (p < 0.01) content in varicose veins (both affected and unaffected segments) as compared with normal saphenous veins were observed. The collagen type III (CIII) and collagen type V (CV) content of varicose veins were found to be slightly reduced as compared to normal veins and consequently the CI/(CIII+CV) ratio in varicose veins increased significantly (p < 0.02) as compared to normal veins. Elevation of the CI/(CIII+CV) ratio in varicose veins may cause considerable weakening of the venous wall, further supporting the "weak wall" theory of varicose vein etiology.