Measles virus hemagglutinin epitopes were analyzed using nine monoclonal antibodies (MAbs) in competitive binding assays (CBA) and by in vitro selection of antigenic variants. In CBA the nine MAbs formed four different but partially overlapping binding groups. In vitro selected variants were analyzed by radioimmune precipitation assay, hemagglutination inhibition (HI), and neutralization assays. Seven operationally distinct MAb antigenic sites could be delineated: two sites were defined by two MAbs to each and five sites by single MAbs. Variants which had lost reactivity to different combinations of MAbs were generated by a branched sequential selection procedure. The most epitopically modified variants had lost reactivity in all assays to eight MAbs. None of these variants showed any major changes in hemagglutination nor neurotropism per se. Only minor changes were detected by HI in reactivity of these variants with human measles antiserum indicating that the epitopic changes were not of major epidemiological significance at least in terms of HI.