Girardinichthys viviparus is a Mexican endangered endemic fish species living only in Lake Texcoco (LTX), one of two extant type localities for this species. The other type locality is Lake Zumpango (LZ). LTX and LZ are fed by wastewater treated at secondary level that contains several endocrine disrupting chemicals. Our goal was to assess the estrogenic and anti-estrogenic effects elicited in G. viviparus by water from the two type localities and by these same matrices enriched with PCBs in order to understand potential damage due to increased xenobiotic levels. Estrogenic and anti-estrogenic effects were evaluated in vitro by E-screen assay in MCF-7 cells and cytotoxicity by MTT assay. PCBs were quantified in type localities. In vivo vitellogenin (VTG) induction was determined by a hybrid ELISA in adult laboratory-born fish exposed during 1, 2, 4, 8 and 16 days to LTX or LZ water in static exposure systems, and by the same matrices enriched with PCBs. We found PCBs only in LTX, but the water from both type localities elicit estrogenic and anti-estrogenic effects in vitro. Cytotoxicity was not observed in MCF-7 cells exposed to LTX or LZ water. VTG induction was higher with LTX water than with LZ water; also the response of males was greater than in females. In the PCB-enriched matrices, VTG induction in both sexes exposed to LTX water was reduced compared to un-enriched matrices. Thus, the sublethal increases in PCB levels may be hazardous to both sexes since they are linked probably to hepatotoxicity.