Potential energy surfaces for rotations of ribose about the nicotinamide N-C bonds in NAD+ and NADH have been evaluated from ab initio molecular orbital calculations with the 3-21G and 6-31G* basis sets. In the optimal conformation of NAD+ the glycosidic C-O bond is near the plane of the nicotinamide ring. By contrast, the lowest energy conformer of NADH has the glycosidic C-O bond nearly perpendicular to the dihydronicotinamide ring. The redox potential of the NAD+/NADH couple is a function of the ribose orientation. There is boat-like puckering of the 1,4-dihydropyridine ring, and the direction of the puckering is anti to the glycosidic bond. The geometry of the transition structure for hydride transfer is similar to that of NADH. When NADH is in the anti conformation, the transfer of the pro-R hydrogen is preferred, and when NADH is in the syn conformation, the transfer of the pro-S hydrogen is preferred.