Heat-stable enterotoxin induces diarrhea by activating guanylate cyclase (GC-C) on enterocytes, resulting in the secretion of water into the intestinal lumen. This study shows that an activating mutation affecting GC-C also produces this effect. Chronic diarrhea is a health problem that poses challenges with respect to both diagnosis and treatment. The irritable bowel syndrome affects 15 to 20% of adults and is a common cause of diarrhea. 1 Other causes include inflammatory bowel disease, infections, paraneoplastic hormones, celiac disease, malabsorption syndromes, and bacterial overgrowth in the small intestine. 2 In addition to organic causes, psychological factors have an important effect on bowel function. 1 Recent studies have focused on the importance of genetic factors in the development of chronic diarrhea 3 – 5 because genetic factors can provide insight into the pathophysiology of intestinal diseases and point to new . . .