Just as there is concern that exposure to environmental estrogens may result in endocrine disruption in mammalian species, there are similar concerns regarding fish and other wild-life species. In this chapter, we review the means for assessing estrogenic activity in fish; these methods exploit physiological mechanisms of hormone receptor interaction, sexual differentiation, and oviparity in fish. We describe a channel catfish (Ictalurus punctatus) model for vitellogenin (VTG) induction in which fish were exposed to chemicals in an acute, single injection paradigm and were monitored for VTG in the serum. To validate the model, we we present data for VTG induction by several xenobiotics with known activity at the mammalian estrogen receptor as environmental estrogens. Results are also presented in which the model was used to demonstrate interference of the normal responce to estradiol by co-adminstrating doses of xenobiotic with estradiol. Finally, we describe a technique in a small fish species, Japanese medaka (Oryzias latipes).