Effects of Cu and Zn on estradiol-17$eta$-Induced vitellogenin (VTG) production were electro-phoretically examined in hepatocyte cultures of rainbow trout. Hepatocytes were precultured for 2 days and then Cu ($10^{-5}$ ~$10^{-4}$M) and Zn ($10^{-5}$~$10^{-3}$M) were added to the incubation medium with estradiol-17${eta}$ ($2{ imes}10^{-6}$M). The hepatocytes were cultured for 5 more days. The relative VTG production rate was expressed as the percentage of VTG to total proteins including the VTG. The addition of CU and Zn to the incubation medium had no appreciable toxin effect on the viability of hepatocytes in the culture. However, Cu markedly reduced VTG production at any concentration used. Zn also specifically reduced VTG production by hepatocytes in a concentration dependent way and there was a significnt reduction at Zn concentrations of $10^{-3}$M. The reduction recovered by removing Zn from the media, but Cu did not. Additionally, enriched Ca concentrations (1.8 to 2.5 or 5.0 mM) in the incubation medium had no protective effect on the reduction of VTG production by Cu $10^{-4}$ M. These results suggest that the production of VTG is more susceptible to Cu and Zn than are other hepatocyte-derived proteins.