In the past 15 years, anomalies of male sexual differentiation have greatly increased in both wildlife and humans in different parts of the world. Environmental endocrine disruptors have been implicated in the dramatic rise in neonatal ambiguous genitalia with variable rates of severity, such as micropenis, cryptorchidism, and isolated or associated hypospadias. Because most environmental pollutants, such as organochlorine pesticides, polychlorinated biphenyls, dioxins and furans, alkylphenol polyetholyethoxylates, and phytoestrogens and phtalates, have estrogenic and antiandrogenic activity, they are able to interfere with normal fetal male sexual differentiation. In a neonatal screening program of ambiguous genitalia, we had the opportunity to evaluate three newborns with male pseudohermaphroditism (MPH) whose mothers were exposed to endocrine disruptors during pregnancy. All had normal testosterone production after human chorionic gonadotrophin stimulation testing, suggesting androgen resistance or so-called idiopathic MPH. Sequences of the 5alpha reductase and androgen receptor genes were normal. Since environmental pollutants are known for their estrogenic activity and can be released progressively from the adipose tissue where they accumulate, we detected their presence by measuring the estrogenic bioactivity of the newborns' serum with a recently developed ultrasensitive bioassay. We found higher estrogenic bioactivity in these newborns than in controls. In conclusion, the maternal exposure to environmental pollutants during pregnancy and high estrogenic bioactivity in the newborns' serum highly suggest that ambiguous genitalia are related to fetal exposure to endocrine disruptors.