Altered baby hamster kidney (BHK-R) cells were serially cultured in the continuous presence of hemagglutinating virus of Japan (HVJ). These cells showed a distinct resistance to superinfection with the homologous HVJ. This resistance of BHK-R cells gradually disappeared after serial passages in the presence of ultraviolet-irradiated HVJ particles which lost infectivity but still preserved hemagglutinating and neuraminidase activities. When BHK-R cells were serially cultured in the presence of a temperature-sensitive mutant of HVJ at non-permissive temperature, the cells also lost the resistance. The resistance of BHK-R cells remained unchanged, even after prolonged incubation in virus-free maintenance medium under the conditions of no cell division. It was suggested that killing of virus-sensitive cells, which were generated during cell proliferation, was required for maintenance of the resistance.Altered baby hamster kidney (BHK-R) cells resistant to HVJ infection have been established and characterized (7,8). The BHK-R cells have been serially cultured in the presence of HVJ. This cell line is distinguishable from persistentlyor transiently-infected cells by the absence of virus and virus-specific antigens. The resistance phenomenon observed in BHK-R cells is restricted to the homologous HVJ, and the cells remain susceptible to infection with other myxo-and paramyxoviruses. No interferon is involved in this resistance. The sialic acid content of BHK-R cells is approximately half that of normal BHK cells, and the process of adsorption and penetration of challenge virus HVJ is restrained. After serial passages in HVJ-free medium, BHK-R cells become susceptible to the HVJ infection with a corresponding increase in sialic acid content of the cells. It has been suggested that the neuraminidase of HVJ particles added to the culture seems to split of sialic acid residues present on the cell surface which are responsible for virus receptor function (1,2,10,14,15), resulting in the induction of the resistance. The present study was performed to obtain more detailed information on the interaction between cell membrane of BHK-R cells and HVJ particles.