The present invention provides methods for treating diarrhea-predominant irritable bowel syndrome comprising administering to a patient in need thereof, an inhibitor of chloride-ion transport in an amount sufficient to treat diarrhea-predominant irritable bowel syndrome (d-IBS). Treatment of d-IBS includes the treatment of the diarrhea component of d-IBS as well as the pain, abdominal discomfort and other symptoms associated with d-IBS. In one embodiment, the inhibitor of chloride-ion transport is crofelemer.