Abstract: The invention provides methods and compositions for increasing Na ion transport and/or epithelial fluid transport in a vertebrate by administering an effective amount of haptoglobin or haptoglobin and hemoglobin. The invention also provides a new therapeutic approach for treating disorders associated with insufficient epithelial Na ion and/or fluid transport, the use of an effective amount of haptoglobin, or haptoglobin and hemoglobin in the preparation of medicament for increasing epithelial Na ion transport in a vertebrate as well as a method of screening a candidate compound for its ability to modulate haptoglobin or haptoglobin and hemoglobin stimulation of epithelial Na ion transport.