A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome. Sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine (Periactin, Merck, Sharp & Dohme, West Point, PA) at maximum tolerable doses that ranged from 12 to 48 mg daily. Usual side effects were mild sedation and dry mouth, but three patients found it impossible to sustain treatment due to nausea and vomiting. Most patients had significant relief of diarrhea, frequently associated with weight gain. Relief of flushing was uncommon. The therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5-hydroxyindoleacetic acid (5-HIAA) excretion in these patients was not reduced. Although there have been case reports of objective tumor regression with cyproheptadine therapy, this was not observed in any of these 16 patients. Cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome. An appropriate initial total daily dose is 0.4 mg/kg divided in three fractions with prompt modification to produce minimal and tolerable side effects. 