Objective: Although serial amnioreduction has substantially improved the prognosis of twin-twin transfusion syndrome, the majority of recipient twins develop cardiac dysfunction in utero and some have structural abnormalities in the neonatal period. The mechanism of cardiac dysfunction is unclear. To test the hypothesis that this occurs as a result of preload or pressure overload, we determined atrial natriuretic peptide and brain natriuretic peptide levels and their association with endothelin-1 in monochorionic pregnancies with or without chronic twin-twin transfusion syndrome. Patients And Methods: Matched maternal and fetal blood samples were obtained in utero from monochorial twin pregnancies complicated with (n = 14) and without twin-twin transfusion syndrome (n = 6). Serial fetal echocardiography assessment included cardiac anatomy, chamber size, cardiothoracic ratio, ventricular thickness, and the presence and severity of atrioventricular valve regurgitation. Postnatal echocardiograms were obtained on the surviving twins. The plasma levels of atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 were measured by use of radio-immunoassay. Results: Levels of fetal atrial natriuretic peptide (P <.001), brain natriuretic peptide (P <.001), and endothelin-1 (P <.001) in the recipient fetuses were higher than in donor twins. Fetal concentrations of atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 in the donor twins were similar to those concentrations in twins that did not have twin-twin transfusion syndrome. Fetal brain natriuretic peptide (P <.01) and endothelin-1 (P <.01) levels were significantly higher in the recipient fetuses when compared to those without severe cardiac dysfunction. A significant positive correlation was present between levels of fetal brain natriuretic peptide and endothelin-1 (y = 230.9 LOG(x) - 264.1, r =.82; P <.01). In contrast, there was no association between levels of fetal atrial natriuretic peptide and the severity of cardiac dysfunction, or with levels of fetal brain natriuretic peptide and endothelin-1. Conclusion: Fetal natriuretic peptide levels were higher in the recipient twins than the co-twins, and the severity of cardiac dysfunction was related to levels of brain natriuretic peptide. These data, thereby, suggest that brain natriuretic peptide is a sensitive surrogate biochemical marker of cardiac dysfunction in the recipient twin. (Am J Obstet Gynecol 2002;186:121–7.)