Abstract Calorimetric measurements of heats arising from transferring Tobacco Mosaic Virus Nucleic Acid (TMV-RNA) from a low to high ionic strength value show that such transfers result in considerable amounts of exothermic heat. Furthermore, the heats measured were found to increase with increasing ionic strength. Velocity sedimentation and viscosity measurements show that in solutions of ionic strength greater than 0.1, the sedimentation coefficient and specific viscosity values of TMV-RNA remain practically unchanged, suggesting that changes in molecular size and hydrodynamic characteristics cannot fully account for the observed heat effects. Optical Rotatory Dispersion (ORD) and Circular Dichroism (CD) measurements of TMV-RNA solutions were made as a function of ionic strength. These studies show that the structure increases with ionic strength. Therefore, conformational changes, mostly as a result of increase in base-pairing and possibly to a smaller extent as a result of changes in base-stacking, appear to be responsible for most, if not all, of the observed heat effects. Energy calculations using the calorimetrically measured heat values show that the energy associated with the conformational changes in TMV-RNA arising from a change in ionic strength from 0.01 to 0.8 is about −2 kcal/mole and this is of the right order of magnitude.