During sexual differentiation there are a number of critical periods when the reproductive system is uniquely susceptible to chemically-induced perturbations. At these times an inappropriate chemical signal can result in irreversible lesions that often result in infertility, whereas similarly exposed young adults are only transiently affected. The serious reproductive abnormalities that resulted from human fetal exposure to DES, synthetic hormones and other drugs provide grim examples of the types of lesions that can be produced by interfering with this process. Furthermore, it is of concern that many of the abnormalities are not expressed during fetal and neonatal life and only become apparent after puberty. The present discussion selectively reviews a wide range of chemically-induced abnormalities of the sexual differentiation in mammals. The list of known developmental reproductive toxicants includes a broad spectrum of drugs, pesticides and toxic substances. Some of the xenobiotics, like the PCBs and dioxin, are of particular concern because they persist in the environment and bioaccumulate in the food chain.