Oral administration of isotretinoin (13-cis-retinoic acid) (6 mg/kg per day), 0.05% hexachlorobenzene (HCB) or both drugs simultaneously for 10 days to female Wistar rats caused a statistically significant induction of aminopyrine-N-demethylase (ADM), 7-ethoxyresorufin-O-deethylase (7-ERO-D) and erythromycin-N-demethylase (EMDM) in the liver microsomes. Oral administration of isotretinoin alone or together with HCB induced a marked induction of 7-ERO-D and EMDM in the skin. Administration of isotretinoin alone for 60 days resulted in the induction of EMDM in the liver microsomes, and in combination with HCB caused a statistically significant induction of all hepatic isozymes. HCB alone caused a marked induction of only 7-ERO-D in the skin. These results clearly show that oral isotretinoin is capable of inducing hepatic and cutaneous microsomal P-450-dependent catalytic activities. It remains to be elucidated whether the induction of these enzymes is of importance for the therapeutic action of isotretinoin.