The early literature on the specificity of the immunological types of foot-andmouth disease virus included references to minor antigenic differences which occurred between strains of virus of the same type. Such strains were called variants. The value of these observations, however, was limited by the techniques then available for differentiation. Bedson, Maitland & Burbury (1927) applied an in vitro serum neutralization test in their comparison of two strains of virus of Type A. They recorded results which indicated that higher serum neutralization titres were obtained with homologous serum-virus mixtures than with heterologous mixtures.Progress in this field of investigation resulted from the development of the complement fixation test. Traub & M6hlmann (1946) used this test to demonstrate antigenic differences between three strains of virus of Type A and also drew attention to the possible significance of these observations in relation to the efficiency of protection by vaccines. Subsequent work at this Institute was directed to the correlation of the results obtained by cross-vaccination, cross-serum neutralization and cross-complement fixation tests. In the first of these experiments Galloway, Davies & Smith, 1962;Hyslop, Davie & Carter, 1963; and unpublished work) has confirmed that there are strains of virus of the same immunological type which can be classified as antigenic variants or subtypes within the types and that in general there is good correlation between the results of the three tests. The results of the two serological tests and the cross-vaccination tests showed that three of the ten pairs were of the same subtype and that seven of them were dissimilar.It has been found that the reproducibility of the results obtained in the complement fixation test and its convenience are of advantage when a large number of strains of virus of one type have to be examined. The complement fixation test was applied by Traub & M6hlmann (1946) to demonstrate differences in the titre of immune sera reacting with homologous and heterologous antigens. used the amount of complement fixed as a measure of such reactions, while Graves (1960) combined the titration of complement with the titration of antisera in order to compare homologous and heterologous antigen-26 Hyg. 62, 4