Guanosine in water self-associates into stable structures, made by four-stranded helices composed of stacked guanosine tetramers. High-pressure synchrotron X-ray diffraction was used to investigate helix stability and energetics in the hexagonal phase. An unusual lateral interhelix negative compressibility was found, indicating that a redistribution of water inside the cell occurs during compression and enforcing the original hypothesis that in guanosine phases water separates into different regions. Moreover, changes in free energy were calculated, and helix elastic constants were derived.