Activities of hepatic monooxygenase systems (aminopyrine N-demethylase, benzo[a]pyrene hydroxylase and p-nitrophenetole O-deethylase) of the brown trout (Salmo trutta), leopard frog (Rana pipiens) and garter snake (Thamnophis) were observed to be considerably lower than those of the rat. The specific activities of their P-450 cytochromes relative to rates of product formation were also much lower than those of the rat, except benzo[a]pyrene hydroxylation by frog microsomes, in which case, the value was about the same as that for the rat. 2. The monooxygenase systems of the trout, frog and snake were identified as cytochrome P-450 systems by the inhibitory effects of carbon monoxide, SKF 535-A, alpha-naphthoflavone and by the requirement for NADPH. 3. NADH synergism of NADPH-supported monooxygenase activities of hepatic microsomes of the trout, frog and snake suggest the participation of cytochrome b5 in these reactions. For the trout, p-nitrophenetole metabolism was supported almost as well by NADH as by NADPH, which suggests that in this species, cytochrome b5 may play an important role in certain monooxygenase reactions. 4. Qualitative differences in the P-450 cytochromes of the trout, frog, snake and rat were indicated by differences in the inhibitory effects of SKF 525-A and alpha-naphthoflavone on monooxygenase activities.