The effects of octylphenol (OP) on vitellogenin production and cell death in hepatocytes from brown bullhead catfish (Ameriurus nebulosus) were studied. Production of vitellogenin was induced in hepatocytes exposed to 10 to 50 μM OP, whereas a higher concentration of OP (100 μM) induced apoptotic cell death. By 3 h after the addition of 100 μM OP, dying cells showed chromatin condensation and DNA fragmentation as determined by fluorescence microscopy and gel electrophoresis. Later stages of cell death (nuclear membrane breakdown and cell fragmentation into apoptotic bodies) were identified in cells exposed to OP for at least 6 h. Hepatocytes exposed to 100 μM OP also produced less vitellogenin than cells exposed to 50 μM OP. An estrogen receptor antagonist, tamoxifen, greatly decreased vitellogenin production in OP-exposed hepatocytes from male fish but did not decrease cell death in these cells. Thus, although the ability of OP to induce vitellogenin production is likely mediated through interactions with the estrogen receptor, the induction of apoptotic cell death by OP does not appear to be dependent on its estrogenic activity but may be a more general toxic effect.