A conformational energy map for a tetrahydropyran-tetrahydrofuran analogue of sucrose was calculated with ab initio quantum mechanics. Geometries were optimized at the HF/4-21G level, using the MIA approximation. The highest energy (with the exception of trichlorogalactosucrose) corresponding to a conformation of an observed crystal structure was for the sucrose moiety in crystalline raffinose. It was less than 1.5 kcal/mol above the local minimum occupied by sucrose, and calculations with larger HF basis sets converged at an energy difference of 2.9 kcal/mol. On the other hand, MM3(92) energies for the raffinose conformation are improbably high, 7 or 8 kcal/mol above the global minimum, whether or not the galactose residue is included in the calculation. Intra- and intermolecular MM3 forces in a miniature model of crystalline raffinose pentahydrate were unable to account for the observed conformation. Also, other observed crystalline sucrose conformations correspond poorly to low-energy regions on MM2, MM3, and other molecular mechanics surfaces. About 6 kcal/mol of the 8 kcal/mol difference in conformational energies comes from the torsion angles involving the anomeric center on the furanose ring. This suggests that even MM3, which has been very successful in modeling other disaccharides, miscalculates the energies of compounds that have overlapping anomeric sequences.