In this study the risk of thrombosis in the portal venous system was assessed in patients with chronic variceal bleeding undergoing sclerotherapy. Twenty-two patients with cirrhosis were prospectively studied with angiography before initiation of sclerotherapy and at mean (+/- SD) 26 +/- 17-month (range, 8-63 months) follow-up. Sclerotherapy consisted of flexible endoscopy, intravariceal and paravariceal, using sodium morrhuate (1.5%-2%) and sodium tetradecyl sulfate (0.5%-1.5%), to obliteration. The mean number of sessions was 6.5 +/- 2.2 (range, 3-11), with a mean total amount of sclerosant of 62 +/- 25 mL (range, 25-112 mL). No patient developed splenic or portal vein thrombosis as shown by arteriography. The flow patterns of portal perfusion, vessel size, and coronary vein visualization showed no significant change. Only one patient had spontaneous reversal of portal flow. Splenic vein histology, examined in five patients in whom sclerotherapy failed and who required shunt surgery, was not significantly different from that in eight patients who had no prior sclerotherapy. It is concluded that under the conditions of the current study, chronic sclerotherapy did not increase the risk of thrombosis in the portal venous system and did not significantly alter the histology of the portal hypertensive splenic vein.