The sensitivity of three genetic lines of Japanese quail to polybrominated biphenyls (PBBs) was evaluated using criteria of egg production, reproduction, and induction of the hepatic microsomal mixed‐function oxidase (MFO) system. Two genetic lines of quail, developed to diverge in their plasma cholesterol response to exogenous adrenocorticotropin (ACTH) (a “Low” line and a “High” line), were compared to a random‐bred line (“Random”). ACTH administration caused increases in plasma cholesterol in the Low line that were 15 and 39% below the Random‐line values in males and females, respectively, while High‐line values were 31% higher in males and 36% higher in females when compared to the respective Random‐line values. Hepatic activities of aryl hydrocarbon hydroxylase (AHH) and hexobarbital hydroxylase (HxH) were not significantly influenced by ACTH administration or by genetic line in either sex. PBBs fed at 40 or 80 mg/kg diet for 5 wk resulted in significant increases in hepatic AHH and aminopyrine N‐demethylase (APND) activities and cytochrome P‐450 concentrations. The induction of AHH, APND, and cytochrome P‐450 was significantly less in Low‐line males in comparison to Random‐ and High‐line males, while the induction of AHH was less in Low‐line females when compared to females from the other two lines, based on covariance analysis. In terms of reproductive parameters, there was a greater adverse effect on egg production at 80ppm PBBs in Low‐line females when compared to the Random and High lines. These data indicate an example in which the biological toxicity of a compound and the induction of a 3‐methylcholanthrene‐type hepatic enzyme are not directly correlated.