Mammalian tissue slices under anaerobic conditions utilized more ribose 5-phosphate than with oxygen due to greater leakage of the enzymes from the cell into the incubation medium. Apparently cytolysis is not the mechanism, for no obvious morphological differences were observed between cells incubated with or without oxygen and non-incubated cells. Probably ribose 5-phosphate does not penetrate the mammalian cell membrane since this substrate was never utilized without leakage of enzymes. Study of the oxygen uptake and aerobic lactic acid formation by mammalian tissue homogenates showed that rabbit kidney was the only tissue in which the addition of ribose 5-phosphate alone greatly increased the respiration and lactic acid formation. Addition of ADP further increased the lactate formation only in rabbit kidney. Attempts were made to explore possible mechanisms to account for these results. DPN was the most important cofactor to stimulate respiration in most of the tissue. Its effects on lactic acid formation from ribose 5-phosphate was variable, but in guinea-pig kidney it produced a great increase if nicotanamide was also added. This is apparently due to the high content of DPN nucleosidase in this tissue as shown by preliminary results. The effect of different combinations of DPN, ADP and cytochrome c on respiration and lactic acid formation were also investigated. © 1961.