The discovery of a ‘stuck twin’ during an ultrasound examination has often been equated with twin-to-twin transfusion based to a great extent on postnatal confirmation of discordant fetal size and hemoglobin concentration. However, the diagnosis of twin-to-twin transfusion cannot be made with certainty after birth since virtually all monochorionic gestations have placental anastomoses and there are many causes of growth deficiency and abnormal hemoglobin concentration. The purpose of this study is to investigate the pathophysiology of chronic twin-to-twin transfusion syndrome and apply the findings to the development of a anagement algorithm. In 42 twin gestations with stuck twin associated with acute hydramnios, we performed targeted ultrasound cordocentesis in each fetus and therapeutic amniocentesis. The diagnosis of chronic twin-to-twin transfusion syndrome required: sonographic evidence of monochorionicity; rapid reaccumulation of fluid after amniocentesis; discordant fetal size, and divergent fetal hematocrit measurements with at least one above or below the 95% confidence interval for gestational age. These criteria were met in 20 of 42 (48%) pregnancies. The mean gestation was 23.8 ± 2 weeks (range 21-27 weeks). In 4 pregnancies, the transfer of adult RBCs from the donor to the recipient was documented. Monochorionicity was confirmed in all postnatally. All recipients had polycythemia and hyperproteinemia. Hydrops developed only in the recipient twin (6 of 20) and was associated with an elevated umbilical venous pressure. All pregnancies were treated with aggressive serial therapeutic amniocenteses. There was no objective evidence that amniocentesis altered the magnitude of the shunt. In addition, 1 patient chose pregnancy termination, 3 a selective fetocide of the donor twin, and 4 transfusion therapy. The mean gestation at delivery was 29 + 4 weeks and the perinatal mortality rate 58% (23 of 40 fetuses). Survival was significantly lower when symptoms appeared < 25 weeks (10 of 30 vs. 7 of 10, p = 0.04). The presumptive diagnosis of twin-to-twin transfusion is frequently erroneous and an accurate diagnosis required antenatal evaluation. Hydrops results from heart failure secondary to a combination of polycythemia and hyperproteinemia. Because no antenatal therapy is clearly effective and the likelihood of neonatal survival is greater when symptoms first appear ≥ 24 weeks, an invasive evaluation should be limited to those pregnancies which either present < 25 or ≥ 25 weeks with a hydropic fetus.