The association between serotonin (5hydroxytryptamine, 5-HT) and fibrosing syndromes such as the carcinoid heart has intrigued clinicians for years. Yet all attempts to produce similar lesions in experimental animals with chronic administration of 5-HT have failed. If 5-HT per se does not induce cardiac fibrosis, perhaps 5-HT functions only as a "co-factor" in this fibrosis. Our previous experimental data suggest that the hypoadrenal state is such a co-factor in the rat. Recent clinical evidence suggests that plasma bradykinin concentration is markedly increased in certain cases of the carcinoid syndrome. Yet both of these potential co-factors singly and in combination with chronic 5-HT administration failed to produce fibrotic lesions in the rat heart. While the etiology of the fibrotic lesions of the carcinoid syndrome remains unknown, further search for co-factors to 5-HT may prove fruitful.