The major structural polypeptides of measles and canine distemper virus (CDV) were isolated by SDS-polyacrylamide slab gel electrophoresis. Rabbit hyperimmune sera directed against the isolated HA, P, NP, F and M polypeptides were prepared. In addition, rabbit hyperimmune sera directed against purified native internal components of measles virus and against purified virions of measles and CDV, untreated or treated with trypsin, were prepared. These sera were used to study the immunological relationships between measles and CDV in immune precipitation tests with 35S-methionine-labelled extracellular virions and intracellular virus polypeptides and by use of component fixation and mixed haemadsorption tests. An immunological relationship between the M polypeptides was demonstrated with sera against both native partially denatured antigens. A reciprocal immunological cross-reactivity between the NP polypeptides was demonstrated by the use of sera directed against native antigens. However, antisera directed against the NP polypeptides isolated from gels did not show any cross-reaction, indicating that they lacked antibodies against the shared antigenic determinants. The immunological cross-reactivity between envelope components of the two viruses was analysed. A close reciprocal immunological relationship between the F polypeptides was demonstrated by immune precipitation of labelled polypeptides. Immunological cross-reactivity between the HA polypeptides of the two viruses could not be demonstrated by use of the same technique neither with sera directed against denatured antigen nor with sera against native antigen when extracellular denatured 35S-methionine-labelled purified virions were used in immune precipitation. A slight cross-reactivity could, however, be demonstrated with sera against native antigens in immune precipitation tests with 35S-methionine-labelled intracellular antigens. It is concluded that all the major structural polypeptides of measles and CDV show varying degrees of reciprocal immunological cross-reactions. The M polypeptides of the two viruses appear most closely related, whereas the HA polypeptides show the most pronounced differences.