OBJECTIVE Certain patients with portal hypertension develop large esophageal varices, whereas others have small varices, or none. Our objective in this study was to determine whether this variability depends upon the amount of blood derived by peripheral portosystemic collaterals. METHODS Esophagogastroscopy to determine presence and size of esophageal varices, and pre-rectal portal scintigraphy to assess portosystemic shunt index (PSI) in inferior mesenteric vein were performed in 45 cirrhotics and 17 patients with pre-cirrhotic liver disease. RESULTS Patients with cirrhosis had higher PSI than normal controls (67 +/- 4 vs. 8 +/- 2%; p < 0.0001) and pre-cirrhotic patients (vs. 34 +/- 6%; p < 0.0001). Neither variceal size nor PSI was correlated with Child-Pugh classification or hepatic venous pressure gradient. PSI was not related to the presence of varices or their size. On the other hand, patients with variceal hemorrhage had elevated PSI, compared with non-bleeders (80 +/- 4% vs. 59 +/- 6%; p < 0.005). CONCLUSIONS This study shows that portosystemic collaterals in the inferior mesenteric vein do not prevent the formation of large varices. Furthermore, the magnitude of blood flow through peripheral collaterals might reflect the risk of variceal hemorrhage.