A dose-dependent increase in tyrosine phosphorylation of five hepatic intracellular proteins with approximate molecular weights of 17, 21, 27, 29, and 34 kDa was seen 24 h after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to C57BL/6J female mice. The ED50 values for tyrosylphosphorylation of these five proteins, respectively, were 0.26, 0.21, 0.26, 0.31, and 0.38 micrograms TCDD/Kg. TCDD induction of 7-ethoxyresorufin O-deethylase activity (EROD) was characterized by an ED50 of 2.5 micrograms/Kg. An eighteen h exposure of a human lymphoblastoma cell line (X3) to TCDD increased tyrosylphosphorylation status of ten proteins with approximate molecular weights of 16, 17, 24, 26, 27, 32, 33, 34, 35, and 36 kDa in a dose-dependent manner. The EC50 values for these TCDD-dependent tyrosylphosphorylation ranged from 0.01 to 0.07 nM TCDD. EROD induction by TCDD in X3 cells exhibited an EC50 of 0.14 nM. These data indicate that TCDD alters intracellular protein tyrosine phosphorylation and these changes are more sensitive biological indicators of TCDD exposure than induction of EROD.