Lower concentrations of formaldehyde are required to inactivate the infectivity of the nucleic acid from tobacco mosaic virus than are required to inactivate intact TMV. The amount of formaldehyde bound at half inactivation is about 400 and 20 molecules for one intact virus particle and its separated nucleic acid, respectively. The reaction of formaldehyde with nucleic acid appears to be specific for the amino groups of the bases. However there is little reaction in those cases where the amino groups are believed to be involved in strong hydrogen bonding as exemplified by DNA and the two-strand complex of polyadenylic and polyuridylic acids. The reaction proceeds in two steps, the first leading to a more labile form of binding, whereas after a more extensive reaction most of the formaldehyde becomes firmly bound. The formaldehyde binding of RNA is greatly decreased at higher salt concentration which is taken as evidence that fewer amino groups are free to react under these conditions. A comparison of TMV-RNA with yeast- and liver-RNA preparations shows that the virus nucleic acid is the most reactive towards formaldehyde. The significance of the quantitative evaluation of the formaldehyde binding on the structure of RNA is discussed.