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Background: Simmondsin is a cyanomethylene glycoside, derived from the desert shrub, Simmondsia chinensis. Simmondsin has been reported to produce weight loss and to decrease food intake, an effect that can be blocked by treatment with an inhibitor of cholecystokinin. Study design: Six experiments were conducted on male Sprague-Dawley rats. Results: In two acute experiments where simmondsin was either added to the diet or injected, there was a dose-related reduction in food intake. The CCK, antagonist, lorglumide, did not block the acute inhibitory effects of simmondsin on food intake and simmondsin did not produce conditioned taste aversion. In two chronic feeding studies, the high dose of simmondsin (0.5%) in the diet produced profound weight loss and death in rats. At autopsy, the kidney, heart and liver of the treated animals were larger than the pair-fed animals and there was a marked suppression of the bone marrow elements with severe anemia. Conclusion: Simmondsin is toxic with profound effects on the hematopoietic system. (C) 2000 Elsevier Science B.V. All rights reserved.