Compelling evidence indicates a pivotal role of estrogen in the regulation of development and function of several systems in the male. Among these functions, estrogens promote permanent masculinization, in early stages of development, of brain structures involved in neuroendocrine control of gonadal function and reproductive behaviour. Paradoxically, however, exposure to high doses of exogenous estrogenic compounds during the so- called critical period of brain differentiation results in an array of defects in the reproductive axis that threat male fertility. In the rat, such a period spans from late fetal life to post-natal day 10. In this scenario, the neonatally estrogenized rat emerged as a useful model to evaluate both physiological and pathological effects of estrogens upon sex differentiation. The aim of the present work is to provide a comprehensive review of the deleterious reproductive effects and the mechanism(s) of action of neonatally administered estrogen in the male rat. Specific implications of the experimental model as to initiate the characterization of potential hazardous effects of environmental xeno-estrogens on male fertility will be discussed.