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The effects of synthetic cyclic somatostatin 14 were studied in two patients with the carcinoid syndrome. The 3-hour intravenous administration of somatostatin (250 micrograms X h-1), a) resulted in the disappearance of flushing in the first patient but was without any clinical effect in the second subject who remained chronically colored; b) lowered plasma levels of motilin, prostaglandins (E1, E2 and F2 alpha) and to a lesser extent of catecholamines in both patients whereas the serotonin level was not altered; c) was followed by a rebound effect with recurrence of severe flushing in the first patient and was associated with a dramatic increase of prostaglandin, substance P and catecholamine levels in both patients. The inhibitory effect of somatostatin and the occurrence of a rebound effect at the end of infusion were confirmed by infusing somatostatin (6 mg per day) during 48 h in the first patients. These results: a) show that somatostatin is an effective drug in carcinoid syndrome with severe flushing; b) confirm that several mediators are affected in carcinoid syndrome. However it could not be excluded that increased circulating levels of prostaglandins, substance P and catecholamines may represent unrelated secondary events; c) suggest that somatostatin primarily inhibits the release rather than the synthesis of tumor products. Owing to the severity of the rebound effect, treatment of the carcinoid syndrome with somatostatin must be undertaken with precaution until specific long-acting analogs are available.