Commercial preparations of serum intended for use in cell and tissue culture medium have the ability to reduce both NAD and NADP. This activity appears to be enzymatic in nature since it requires a non-dialyzable, heat-sensitive component. Dialysis of serum against physiological NaCl completely abolished endogenous activity which could again be restored by the addition of ultrafiltrates of serum or specific substrates such as lactate, malate or isocitrate. Comparative studies show this property to be generally universal in serum of various species prepared by different commercial suppliers. Of interest is the fact that considerable dehydrogenase activity for both NAD and NADP still remains after heat treatment at 56°C for 30 minutes. This point is discussed with references to the implications to mammalian cells and tissues cultured in artificial medium in which serum is a component. © 1969.