Poliovirus and foot-and-mouth disease virus (FMDV) initiate infection by binding to specific cell surface receptors, which is followed by a poorly understood disassembly process. To probe these early steps of infection, the ability of poliovirus and FMDV to infect cells following binding through an alternative receptor was examined. For these studies, a Chinese hamster ovary (CHO) cell line expressing the B2 isoform of the murine Fc receptor (FcR) was used. Both viruses were able to bind to this cell line in an antibody-dependent manner, but only FMDV was able to productively infect these cells following binding through the FcR. These results suggest that the natural poliovirus receptor has dual functions in binding and destabilizing the virus particle, whereas the putative FMDV receptor may only be necessary for virion binding. These findings are consistent with differences in virion architecture which predict a more intimate virion-receptor association for poliovirus than for FMDV.