Experiments were designed to study functional changes in superficial leg veins of patients with primary varicosity. Excess segments were taken from 19 patients undergoing elective vein resection. Excess segments of greater saphenous veins taken from 13 patients undergoing coronary or lower extremity arterial bypass were used as controls. These rings, some with endothelium deliberately removed, were suspended for the measurement of isometric force in organ chambers. Segments of veins were also evaluated with respect to their total protein content, endothelin content, and histologic structure. In varicose veins, maximal contractions in response to potassium chloride (n = 9), norepinephrine (n = 9), and endothelin (n = 4) were reduced 71.1%, 78.2%, and 75.6%, respectively, compared with contractions in control veins (p < 0.01). In addition, no differences were detected in the maximal tension or tissue sensitivity (EC50) between segments of nonvaricose greater saphenous vein and adjacent varicose tributaries from the same patient. Rings with and without endothelium contracted similarly. In varicose veins, endothelium-dependent relaxations produced by the calcium ionophore A23187 were attenuated 89.7% compared with relaxations in controls (n = 6, p < 0.01). In veins from patients with primary varicosity, endothelium-independent relaxations produced by nitric oxide (n = 6) and forskolin (n = 3) were diminished 86.8% (p < 0.01) and 65.6% (p < 0.05), respectively, compared with relaxations in control veins. In primary varicose veins, protein content was decreased (n = 17, p < 0.01) and endothelin content increased (n = 17, p = 0.1) compared with those values in control veins (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)