A study was made of the fixation of complement by antigens of foot-and-mouth disease virus ( FMDV). The technique was applied to the determination of the serological properties of FMDV antigens and to the differentiation and classification of strains. An examination was made of the relationships between antigen, antibody and the fixation of complement. Complement fixation (C F) with FMDV followed the same principles as models developed in other antigen/ antibody systems. The assumption that there is a relationship of direct proportionality between the amount of complement fixed and the amount of antiserum reacting with constant antigen, was found to be incorrect. An alternative method was proposed for the quantitative differentiation of FMN strain. Applying this method, isolated FMDV antigens were examined for type and sub-type specificity. The intact virion was type specific and possessed considerable sub-type specificity. In contrast, capsid sub-units reacted heterotypically and with less sub-type specificity. A non-structural virus infection-associated antigen had virtually no Eype or sub-type specificity. Empty capsids were shown to possess the same sub-type specificity as intact virions, while trypsin-treated virus was more cross-reactive. The implications of the serological activity of these antigens were discussed, in relation to the structure of the virion and to the application of CF to routine typing and subtyping procedures. The CF test was compared to cross-protection and cross-neutralisation tests for the determination of differences between strains and found to produce similar results. A large number of strains of one type were compared in cross-CF tests and from the results it was shown that the present methods of sub-type classification are unsatisfactory. A new system for the sub-type classification of FHDV strains was proposed.