This study examines biochemical and hormonal responses in resident and migratory fish from the New York-New Jersey (USA) Harbor Complex (NY-NJHC) and those treated with sediment-associated organic contaminants. Following laboratory exposures to organic extracts of NY-NJHC sediments (injection), livers from adult male mummichogs, Fundulus heteroclitus, were analyzed for vitellogenin (VTG), cytochrome P4501A (CYP1A), CYP3A, and estradiol 2-hydroxylase (E2OHase) and ethoxyresorufin-O-deethylase (EROD) activities. Levels of CYP1A (311–391% of control) and EROD (267–361% of control) were elevated in mummichogs exposed to high doses of sediment extracts, while VTG, CYP3A, and E2OHase were unaffected. In field studies, reproductively mature male mummichogs collected from a highly contaminated area, Newark Bay (NJ, USA), did not have detectable levels of VTG but did exhibit elevated levels of CYP1A and EROD. Vitellogenin was also not detected in juvenile striped bass (Morone saxatilis) collected from the main stem of the lower Hudson River (NY, USA). Similar to results in the sediment extract- treated fish, CYP3A and E2OHase were unaltered in Newark Bay F. heteroclitus. The lack of response of CYP3A and E2OHase activities to contaminant mixtures, either environment or sediment derived, suggests that compounds in these mixtures either do not alter these enzymes, produce antagonistic effects in mixtures, are present at ineffective concentrations, or are regulated in a species-specific manner.