This study examines the value of assessing inter-twin membrane folding in monochorionic twin pregnancies in the prediction of twin-to-twin transfusion syndrome. In 83 monochorionic twin pregnancies ultrasound scans were carried out at 10-14, 15-17 and 19-21 weeks to investigate folding of the inter-twin membrane as an early sonographic feature of inter-twin discrepancy in amniotic fluid volume. There were 23 (28%) cases of membrane folding, which was first observed in one case at 10-14 weeks, in 21 cases at 15-17 weeks and in another case at 24 weeks. In 12 (52%) of the 23 cases the pregnancy progressed to severe twin-to-twin transfusion syndrome and 10 of these were treated by endoscopic laser coagulation of the placental vascular anastomoses. In the other 11 cases there was a moderate syndrome with large discrepancies in amniotic fluid volume and fetal size, persisting throughout pregnancy. In the severe group, five pregnancies resulted in live birth of both babies, three in live birth of one and intrauterine death of the other twin and in four cases there were no survivors. In the moderate group, all babies survived and the inter-twin disparity in birth weight was more than 20%. Similarly, all 60 pregnancies with no membrane folding resulted in live births. In all three groups there was an increase in inter-twin disparity in fetal size with gestation and the greatest inter-twin disparities were in those with moderate twin-to-twin transfusion syndrome from as early as the 10-14 week scan. These findings demonstrate that folding of the inter-twin membrane occurs in about one-quarter of monochorionic twins and in about half of these there is subsequent development of severe twin-to-twin transfusion syndrome.