Right-handed DNA duplexes assume a B form at high water activity and an A form at reduced levels, but the molecular origins of this behavior are in debate. Four large-scale molecular dynamics simulations performed on sodium salts of the A and B forms of DNA [d(CGCGAATTCGCG)] in water and in ethanol/water mixtures form the basis for a molecular level explanation of the origins of environmental sensitivity of DNA conformation. The trends observed in conformational preferences experimentally are accounted for by the calculations. Analysis of the results indicates the free energy associated with the explicit organization of the mobile counterions around the A and B forms of DNA to be the key feature in the resolution of otherwise paradoxical observed trends.