Cytochrome P-450, purified from liver microsomes of phenobarbital-induced rabbits, was phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase. Upon phosphorylation P-450 was found to be converted to its denatured form, P-420, as verified spectroscopically from the CO-bound form of the reduced cytochrome. The conversion was dependent on both kinase and ATP. Thus, cyclic AMP may regulate the biotransformation system through the control of the degradation rate of microsomal P-450 in vivo.