TCCD is a ubiquitous environmental contaminant. Exposure to TCCD result in metabolic, immunologic, reproductive and neoplastic effects in animals. TCDD is a putative human carcinogen and poses a potential risk to human health. We have made the intriguing observation that TCDD up regulates expression of the cytokine inducible isoform of the enzyme nitric oxide synthase and induces nitric oxide biosynthesis by rat hepatic endothelia cells. This is the first demonstration that aryl hydrocarbons regulate an intracellular messenger in the endothelium and provides an important clue on a potential mechanism by which TCCD may alter cellular functioning and induce toxicity. It is our hypothesis that TCDD acts to induce expression of type II no synthase (N0S II) in endothelial cells and that N0 produced in response to TCDD may mediate some of the toxic effects of this contaminant. To test this hypothesis experiments are designed to analyze molecular mechanisms by which TCDD regulates N0 production, and to determine the role of N0 in TCCD-induced tissue injury in rats. These studies will provide information potentially useful for the development of clinical regimens for abrogating TCCD-induced injury in humans. These studies are important and may provide insight into one mechanism by which TCDD induces toxicity.