The results from the present study indicate that rat IFN-gamma decreases hepatic P450 levels and catalytic activities in female rats. The magnitude of the down-regulation of P450 is similar to that found in male rats. Furthermore, the activities of specific P450 isoforms (P4502A1 and P4502C6 and possibly P4502C12, and P4502B1 and 2) are decreased by IFN. Hence, the effect of IFN in female rats appears to involve several, but not all, hepatic P450 isoforms. Both hormone-dependent and hormone-independent isoforms are suppressed by IFN. The mechanism for this effect does not, however, appear to be mediated by changes in serum levels of sex steroids.