||The effects of 3,3',4,4'-Tetrachlorobiphenyl (TCB) were examined in scup (Stenotomus chrysops). A low TCB dose elicited strong induction of hepatic CYPlAl mRNA, protein, and activity. A high TCB dose elicited strong induction of hepatic CYPlAl mRNA, but not of CYPlAl protein or activity. This 'suppression' at the high dose was specific for CYPlAl, and was not seen for other enzymes. In vitro studies indicate that hepatic CYPlAl is inactivated in the presence of TCB plus cofactor, likely due to the production of reactive oxygen species during TCB occupation of the active site. CYPlAl inactivation by TCB in vitro may explain suppression of CYPlAl protein content in vivo. TCB induced CYPlAl content in endothelial and epithelial cells of several organs. Intensity of induction was time-dependent, dose-dependent, and varied among the different organs. TCB treatment caused lesions or cellular alterations in liver, kidney, gill, spleen, and tail fin. 3,3',4,4'-TCB and 2,2',5,5'-TCB were both metabolized by hepatic microsomes from scup, beluga whale, and pilot whale. Studies indicate that 3,3',4,4'-TCB is metabolized by scup CYPlAl and 2,2',5,5'-TCB by the putative scup CYP2B. Studies suggest that 3,3',4,4'-TCB is metabolized by cetacean CYPlA, and that both cetacean species express a possible CYP2B enzyme in liver.