The enzymes involved in the initial degradative steps of lysine metabolism, lysine–2-oxoglutarate reductase and saccharopine dehydrogenase, were studied and their activities in different mammals compared. Values obtained in human, rat, pig, dog, cat, ox and sheep liver indicated that in vitro, appreciable degradation of lysine to saccharopine (4–6nmol/min per mg of protein) occurred. The specific activity of saccharopine dehydrogenase in most species studied was higher than that of lysine–oxoglutarate reductase. The rate of production of glutamate from saccharopine in each animal species was investigated and related to the rate of production of α-aminoadipate. The rate of formation of lysine from saccharopine, catalysed by saccharopine oxidoreductase, was examined and correlated with the dietary intake of lysine in each species studied.