When K562 cells were infected with Newcastle disease virus (NDV) or human parainfluenza type 2 virus (hPIV‐2), polykaryocyte formation could not be detected. Failure of multinucleated giant cell formation in K562 cells infected with either NDV or hPIV‐2 is due to disturbance of the viral envelope‐cell fusion step or to defect in the cell‐cell fusion step, respectively. Especially, NDV completely replicated in K562 cells, and the hemagglutinin‐neuraminidase and fusion proteins expressed on the cell surface of NDV‐infected K562 cell were fully functional for fusion inducing activity. Therefore, the cell membranes of K562 cells are considered to be resistant to virus‐induced cell fusion. Membrane fusion is regulated by many host factors including membrane fluidity, cytoskeletal systems, and fusion regulatory proteins system. An unknown regulatory mechanism of virus‐induced cell fusion may function on the cell surface of K562 cells.