Summary Semliki Forest virus was thermally inactivated between 20° and 50° by two processes, one of which predominated at temperatures below 41° and the other at higher temperatures. At pH 6.5, the rates of inactivation were greater than at pH 7.5 but the nature of the reactions was unchanged. The stability of the virus in phosphate buffer solutions was greatly reduced at lower concentrations of protein in the suspending medium. The rate of inactivation was reduced in the dark. At higher temperatures, a change occurred in the surface properties of the virus that did not, of itself, cause loss of infectivity. It is suggested that at the higher temperatures the inactivation was a consequence of a structural breakdown of a surface unit in the virus; at lower temperatures a more subtle change in the substructure was responsible for inactivation.