An association between the ingestion of tryptophan and a syndrome characterized by scleroderma-like skin abnormalities, fasciitis, and eosinophilia has recently been recognized in the United States. We report the clinical and histopathological findings in nine patients and the results of biochemical analyses of tryptophan metabolism in seven patients with this syndrome. Edema of the extremities, frequently accompanied by pruritus, paresthesia, and myalgia, developed in the nine patients (six women and three men; age range, 30 to 66 years) 1 to 18 months after the start of therapy with tryptophan (1.5 to 3.0 g daily) for insomnia, depression, or obesity. Five patients were taking drugs (benzodiazepines) known to inhibit hypothalamic—pituitary—adrenal function, and one had adrenal insufficiency. All had blood eosinophilia in the acute phase of their illness (mean eosinophil count [±SD], 3.62±2.87×l09 cells per liter). All had histopathological changes in the dermis and subcutaneous tissue typical of scleroderma, and seven patients had eosinophils. The fascia was inflamed and fibrotic, and adjacent skeletal muscle often showed perifascicular inflammation. Tryptophan was discontinued in all patients, and eight received prednisone. The cutaneous symptoms improved, but only two patients had complete resolution of their illness. The patients had plasma levels of tryptophan before and after an oral dose of tryptophan that were similar to those in normal subjects. Plasma levels of L-kynurenine and quinolinic acid, which are metabolites of tryptophan, were significantly higher in four patients with active disease than in three patients studied after eosinophilia had resolved or in five normal subjects (P<0.001) — findings consistent with the activation of the enzyme indoleamine2,3-dioxygenase. This illness resembles eosinophilic fasciitis and probably represents one aspect of the recently reported eosinophilia—myalgia syndrome. The development of the syndrome may result from a confluence of several factors, including the ingestion of tryptophan, exposure to agents that activate indoleamine-2,3-dioxygenase, and possibly, impaired function of the hypothalamic—pituitary—adrenal axis. A RECENTLY described condition termed the eosinophilia—myalgia syndrome has been reported in epidemic form in the United States.1 Case–control studies have established an association between the use of products containing the amino acid tryptophan and the development of the syndrome.2 Although its full spectrum has yet to be defined, it is similar in some respects to a previously described chemically induced illness, the toxic-oil syndrome, which occurred in epidemic form in Spain in 1981,3 and the syndrome of eosinophilic fasciitis. We have previously described a scleroderma-like illness in a patient receiving L-5-hydroxytryptophan and carbidopa that was remarkably similar to the… © 1990, Massachusetts Medical Society. All rights reserved.