The effect of hexachlorobenzene (HCB) on microsomal cytochromes P-450 and b5, monooxygenase activity and membrane composition was examined in male and female Fischer rats. Cytochrome P-450 was induced more in male than in female animals while cytochrome b5 was induced only in males. Analysis of patterns of induction of microsomal monooxygenases showed that aminopyrine-N-demethylase activity doubled in both sexes after treatment while aryl hydrocarbon hydroxylase activity was 16 times the control value in the females and 1.5 times in the males. After HCB treatment the phospholipid content of microsomal membranes per gram of liver was increased in both sexes while cholesterol was unchanged. Analysis of the phospholipids (PL) pattern showed that the percentage of sphingomyelin (SPH) decreased significantly (50% of the control value) while phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) did not change. These changes resulted in a reduction of membrane microviscosity and indicate that HCB interferes with the biosynthesis of phospholipids containing choline. Free fatty acid (FFA) content also dropped in both sexes but females were more affected; free arachidonic acid rose in females. HCB induction of microsomal cytochromes and monooxygenases is thus accompanied by marked modifications of membrane composition. Comparing the 2 sexes, HCB showed more pronounced features of 'PB type' inducers in males.