Epidemiologic and experimental evidence reviewed in this article emphasizes the complex and multifactorial etiology of endemic goiter. The important role of iodine deficiency as an etiologic factor in endemic goiter is firmly established, but there is evidence that other environmental factors can play an equally important role in the pathogenesis of this condition. Chemical categories, sources, and sites of action of the various classes of naturally occurring goitrogens and antithyroid agents are reviewed in this article. Evidence of the presence of these compounds in foodstuffs and drinking water is discussed. Bacterial contamination of water supplies also appears to be important in the development of goiter. Microorganisms appear to intervene in the biosynthesis and degradation of organic goitrogenic pollutants or may induce thyroid growth-promoting activity in the host, or both. Malnutrition and poor socioeconomic conditions, as for iodine deficiency, enhance the action of environmental goitrogens. Thus, a coordinated multidisciplinary approach is essential to solving this public health problem.