The effects of naturally occurring furanocoumarins on cytochrome P-450 have been investigated in rat liver microsomes. Incubation of microsomes with an NADPH-generating system and four furanocoumarins such as imperatorin, isoimpe ratorin, phellopterin and byakangelicin at 37° in vitro resulted in a significant destruction of cytochrome P-450. A single treatment(50㎎/㎏, i.p.) of rats with each furanocoumarin caused a rapid loss of cytochrome P-450 accompanied by the loss of heme from the microsomes but not by the loss of cytochrome b_5. It is suggested that cytochrome P-450 is specifically destroyed by furanocoumarins in a metabolic process involving destruction of its heme group and as a consequence, hepatic enzyme activities are depressed markedly.