Sulfamethazine (SMZ) ip administration for 3 d to chickens showed significant induction of cytochrome P-450 levels and in the activities of aminopyrine N-demethylase, aniline hydroxylase and glutathione 5-transferase at the dosage of 150 mg SMZ/kg body weight. Cytochrome P-450 and the activity of aniline hydroxylase were significantly decreased at 300 mg SMZ/kg body weight when compared to 150 mg SMZ/kg body weight. Other doses produced no significant changes in the parameters studied. One hundred fifty mg SMZ/kg for 1 or 3 d caused significant induction of cytochrome b5, cytochrome P-450, the drug metabolizing enzymes and glutathione s-transferase; however, 5 d of SMZ produced no significant changes. The in vitro 10 mM SMZ inhibition of aminopyrine N-demethylase and aniline hydroxylase and the induction of enzymes at 150 mg SMZ/kg body weight indicates that SMZ is a substrate of the mixed function oxidase system and may be an inducer of specific forms of cytochrome P-450.