At a high dose, cyclophosphamide (Cy, 200 mg/kg) causes depression of the enzyme activity of the hepatic mixed function oxygenase (MFO) system in Sprague-Dawley rats. The present report provides evidence for the early regeneration of the depleted enzyme activity in Cy-treated rats by purified protein A (P) of Staphylococcus aureus. Enzymes of the MFO system, such as aminopyrine demethylase and aryl hydrocarbon hydroxylase, were assayed and the content of cytochrome P-450 was determined. Inoculation of P (60 micrograms/kg) prior to Cy inoculation provides a better effect than P administration after Cy. The exact mechanism of P action is unknown. P-treated animals appear to have an ability to repair the damage caused by the toxic metabolites of Cy earlier than those in the Cy group. This property of protein A may become useful in accelerated regeneration of the enzyme activity in the hepatic MFO system following the toxic insult of Cy metabolites.