Respiratory syncytial virus is the most common cause of lower respiratory tract disease in young children worldwide. The F glycoprotein of this virus is one of the important targets of a protective immune response; however immunity is incomplete and repeated infections occur. Therefore, a major effort of this laboratory has been to construct a detailed epitope map of the RSV F glycoprotein and then evaluate antigenic variation of the F-neutralization and fusion epitopes. The gene for the fusion glycoprotein of the A2 strain of RSV and 14 monoclonal antibody resistant mutants has been cloned and sequenced. Information from over 60 clones has been analyzed in order to identify the amino acids contributing to the epitopes involved in neutralization and fusion. We were successful in determining amino acids that contribute to 5 epitopes in antigenic site A, one epitope in antigenic site AB, 1 epitope in site B and one epitope in site C. Comparison of the deduced amino acid sequence for the monoclonal antibody resistant mutants with F sequences for subgroup A, subgroup B and bovine strains of RSV show that residues involved in most of the site A and C epitopes are conserved among all the strains. This is in contrast to the site B epitope which is located in a hypervariable region. The change in amino acid defined by the site B MARM is likewise changed in the 18537 strain (a subgroup B virus) as well as both bovine strains of RSV. During the next year we propose to evaluate the immune response to RSV F antigenic sites A, B and C following immunization and natural infection.