DNA exhibits a surprising multiplicity of structures when it is packed into dense aggregates. It undergoes various polymorphous transitions (e.g., from the B to A form) and mesomorphous transformations (from hexagonal to orthorhombic or monoclinic packing, changes in the mutual alignment of nearest neighbors, etc). In this report we show that such phenomena may have their origin in the specific helical symmetry of the charge distribution on DNA surface. Electrostatic interaction between neighboring DNA molecules exhibits strong dependence on the patterns of molecular surface groups and adsorbed counter-ions. As a result, it is affected by such structural parameters as the helical pitch, groove width, the number of base pairs per helical turn, etc. We derive expressions which relate the energy of electrostatic interaction with these parameters and with the packing variables characterizing the axial and azimuthal alignment between neighboring macromolecules. We show, in particular, that the structural changes upon the B-to-A transition reduce the electrostatic energy by Ϸkcal͞mol per base pair, at a random adsorption of counter ions. Ion binding into the narrow groove weakens or inverts this effect, stabilizing B-DNA, as it is presumably the case in Li ؉ -DNA assemblies. The packing symmetry and molecular alignment in DNA aggregates are shown to be affected by the patterns of ion binding.We recently suggested a theory of electrostatic interaction between two macromolecules with parallel cylindrical cores and arbitrary surface charge distributions (1). Applied to helical molecules, it explained such puzzling observations as DNA over-winding from 10.5 bp͞turn in solution to 10 in hydrated fibers, counter-ion specificity in DNA condensation, mysteriously small decay lengths of the forces observed over the last 15 Å of separation between DNA, collagen, and four-stranded guanosine helices, etc. We found that all these effects are driven by the helical symmetry of the charge distributions and formulated the corresponding symmetry laws (2).This theory was based on the solution of the linearized Poisson-Boltzmann equation for the electric field created by two opposing macromolecules in electrolyte solution (1). Such model may become invalid at small distances between helices due to effects of the finite size of electrolyte ions and water molecules and due to the breakdown of linear electrostatics. We, therefore, used it to interpret the phenomena observed in ''wet'' DNA assemblies. However, DNA helices in chromosomes, phage heads, and inside some cell nuclei are separated by only one to two monolayers of water. Crystallographic studies of even denser aggregates of natural DNA at Յ90% relative humidity revealed structural poly-and mesomorphism (3, 4), which is still poorly understood.Generally, poly-and meso-morphous transitions are driven by intra-and inter-molecular stresses. Various approaches have been used for evaluation of different components of these stresses in DNA. For an isolated DNA molecule in solution...