A fusing variant of the nonfusing O'Take strain of mumps virus was obtained by growing virus under the selective pressure of the competitive neuraminidase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA). The variant virus, O'Take(DANA)v1, causes extensive syncytial formation in CV-1 cell cultures in contrast to the relatively noncytopathic infection caused by the O'Take virus parent. Neuraminidase assays indicate that O'Take(DANA)v1 has no detectable neuraminidase activity using either fetuin or neuraminlactose as substrate. In addition, the O'Take(DANA)v1 virus can agglutinate red blood cells but cannot elute from these cells once adsorbed. No differences were detected in the biochemical or antigenic structure of the hemagglutinin-neuraminidase (HN) proteins from O'Take virus and O'Take(DANA)v1. These results indicate that the neuraminidase enzyme of the mumps virus HN glycoprotein is involved in modulating the cell fusion cytopathology of mumps virus infections.