Our studies using synthetic neuraminidase substrates have been extended to explore the role of neuraminidase during influenza virus replication. It was found that neuraminidases are required to remove neuraminic acid from virus particles to prevent autoaggregation of the virus. Results supporting this hypothesis were obtained by characterizing temperature sensitive influenza virus mutants defective in neuraminidase. We will continue to study temperature sensitive neuraminidase mutants and attempt to understand the precise role of neuraminidase during virus replication.