Nucleic acid parameters are developed for the all-atom empirical energy function used in the CHARMM program. The parameters were determined by use of results for model compounds, including the nucleic acid bases, dimethyl phosphate and anionic and dianionic methyl phosphate, ribose, and deoxyribose. Internal parameters (bond length, bond angle, Urey-Bradley, dihedral, and improper dihedral terms) were chosen to reproduce geometries and vibrational spectra from experimental crystal structures, infrared and Raman spectroscopic data, and ab initio calculations. Interaction parameters (electrostatic and van der Waals terms) were derived from 6-31G* ab initio interaction energies and geometries for water molecules bonded to polar sites of the model compounds and from the experimentally measured gas phase Watson-Crick base pair energies and geometries, base heats of sublimation, and experimental and 6-31G* ab initio dipole moments. Emphasis was placed on a proper balance between solvent-solvent, solvent-solute, and solute-solute interactions with reference to the TIP3P water model. Tests on nucleic acid base crystals showed satisfactory agreement between calculated and experimental values for the lattice parameters, nonbonded interactions, and heats of sublimation. Base pair variations in stacking energies are consistent with experiment and ab initio dodecamer crystal structures, including water molecules and counterions. Simulations of these systems revealed the parameters to accurately reproduce Watson-Crick base pairing, internal geometries including the backbone dihedrals, sugar puckering and glycosidic linkages, and the hydration of the nucleic acids. The present parameters should be useful for modeling and simulation studies of nucleic acids, including both structural and energetic analysis.