Hexachlorobenzene (HCB) was administered orally (500 mg/kg d) for 1, 2, 5, or 10d) to sexually mature Japanese quail to compare altered hepatic porphyrin levels with changes that occur in hepatic xenobiotic metabolizing enzymes. Porphyrin levels rapidly increased following the administration of HCB (three times control levels after a single dose of HCB), and birds began to develop porphyria (i.e., porphyrin levels were at least 10 times higher than controls) following 5 d of treatment. Following 10 d of HCB treatment, 3 of 4 treated quail were porphyric. Coincident with the HCB-induced disruption of the heme biosynthetic pathway were increases in various hepatic constituents. Changes included elevation of microsomal protein concentrations and increases in the specific content of cytochrome P-450, in the activities of aryl hydrocarbon hydroxylase (AHH), biphenyl hydroxylase (BPH), ethoxyresorufin-O-deethylase (EROD), and ethoxycoumarin-O-deethylase (ECOD), and in cytosolic and microsomal glutathione S-transferase (GSH-t) levels. In addition, the lambda max of the CO versus CO-reduced absorption spectra of hepatic microsomes from HCB-dosed birds showed a hypsochromic shift of 450 to 448 nm. The activity of NADPH-cytochrome P-450 reductase was increased following 10 d of HCB, and the activity of epoxide hydrolase was increased following 5 d of HCB. Most of these changes occurred with a single HCB treatment, and no further alterations developed in the nature of the response with repetitive dosing. Only weight loss, increased cytochrome P-450 content, and increases in GSH-t activity occurred simultaneously with the induction of porphyria.