In this study, we examined the role of the dCAT-1 receptor in syncytium formation and susceptibility to infection by different ecotropic MLVs. We generated an expression vector containing dCAT-1 and transfected either this clone or the mCAT-1 gene into cells of non-rodent species that are not normally infectible by ecotropic virus. The transfected cells were then evaluated for susceptibility to infection by ecotropic MLVs and for virus induced syncytia. While virus induced syncytia were only seen in the dCAT-1 transfectants, a different panel of virus isolates was capable of efficiently infecting and/or inducing syncytia in these transfectants suggesting that virus-cell fusion and cell-cell fusion are distinct receptor mediated phenomena. The possible contribution of differential glycosylation to these phenotypic differences was evaluated using Western analysis, treatment by glycosylation inhibitors and mutagenesis to remove glycosylation sites.