Gonadally mature fish display strong sex-related differences in the content and activity of P4501A, the major polynuclear aromatic hydrocarbon-inducible P450 form in teleosts. Such differences appear related to plasma levels of the female sex steroid, estradiol (E2); however, neither the mechanism of estradiol suppression of P4501A nor the capacity for hormonal regulation to overcome P4501A induction by high concentrations of potent inducers are known. Gonadally mature flounder (Pseudopleuronectes americanus) were collected from Fox Island (FI), Rhode Island, a reference site, and New Bedford Harbor (NB), Massachusetts, a site highly contaminated with polychlorinated biphenyls. Differences in flounder P4501A expression were determined at the level of P4501A catalytic activity (measured as ethoxyresorufin-O-deethylase, EROD), P4501A protein content (immunoquantitated), and P4501A mRNA content (by Northern blot) as they relate to sex, reproductive status and hepatic PCB content. (Copyright (c) 1992 Elsevier Science Publishers Ltd, England.)