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Foot-and-mouth disease (FMD) virus was partially inactivated by several methods: incubation with dilute formaldehyde or acetylethylene-imine, ultraviolet (U.V.) irradiation, heating, or by mixing with type specific antiserum, trypsin or extracts from cells susceptible to the virus. The serological properties of the treated virus preparations were studied by complement-fixation and agar diffusion tests and their content of infective ribonucleic acid (RNA) determined by phenol extraction. The ability of the treated preparations to attach to susceptible cultivated pig kidney cells was examined. The decrease in viral infectivity when FMD virus was treated with formaldehyde or acetylethyleneimine, U.V., or heat at 25° or 37° was proportional to the loss of infective RNA, with little impairment of its serological properties or its ability to attach to susceptible cells. In contrast, loss of viral infectivity on mixing with antiserum, trypsin or cell extracts was due to the failure of the virus to attach to susceptible cells; the viral RNA is still present in an infective form in these mixtures.