Dichlorodiphenyltrichloroethane (DDT) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are complex organic compounds that are frequently found in the environment as a result of agricultural and industrial activities. Both compounds have substantial immune system and endocrine system disrupting activity, acting as estrogen agonists or antagonists (xenoestrogens). Research has demonstrated that exposure to xenoestrogens can result in body weight loss, developmental abnormalities, thymic atrophy, carcinogenesis, and tissue-specific hypoplastic and hyperplastic responses. Although several studies have reported significant adverse effects of these compounds on the endocrine system, very few investigations have focused on the specific mechanisms of action on the immune system. This paper reviews the cellular and molecular mechanisms of DDT- and TCDD-induced toxicity on the endocrine and immune systems, and explores their potential impact on the pathogenesis of immune disease.