The mechanism of Sendai virus fusion was investigated by studying the effect of the dehydrating agent polyethylene glycol (PEG) on the interaction of the virus with erythrocyte membranes. The initial rate of virus fusion, monitored continuously by a fluorescence membrane fusion assay, increases approximately 5-fold in the presence of small amounts (4%, w/v) of PEG. The polymer did not trigger a massive nonspecific fusion event, as the limited number of virus particles that fuse per erythrocyte ghost remains unaltered. A mass action kinetic analysis reveals that the binding rate constant increases approximately 1.5-fold; however, the fusion rate constant is enhanced by about an order of magnitude. The results demonstrate that hydrophobic int...