To evaluate the pathogenesis of the diarrhea of carcinoid syndrome, triple-lumen jejunal-perfusion studies were performed in three patients with carcinoid syndrome and diarrhea and eleven control subjects. In contrast to the net absorption observed in the control subjects during perfusion with an isotonic mannitol-saline solution, net secretion occurred in two of the three carcinoid-syndrome patients. Glucose absorption and glucose-stimulated fluid absorption were normal in the carcinoid-syndrome patients. Methysergide controlled the diarrhea and in one patient net absorption was observed during methysergide therapy. These studies suggest that intestinal secretion may be one of the pathogenetic factors responsible for the diarrhea of carcinoid syndrome and provide additional evidence of the importance of intestinal electrolyte secretion in the genesis of many diarrheal states.