Using a plasmid expression system in HeLa cells, we have previously shown that the fusion (F) protein of simian virus 41 (SV-41) induces cell fusion when coexpressed with the haemagglutininneuraminidase (HN) protein of human parainfuenza virus type 2 (PIV-2), while the PIV-2 F protein does not induce cell fusion with the SV-41 HN protein, In the present study, we found that the PIV-2 F protein induced extensive cell fusion with the HN protein of mumps virus (MuV), whereas the SV-41 F protein did not, Chimaeric analyses of the F proteins of PIV-2 and SV-41 identified two regions (designated M1 and M2) on the PIV-2 F protein, either of which was necessary for chimaeric F proteins to show fusogenic activity with the MuV HN protein, Subsequently, two additional regions (P1 and P2) were identified on the PIV-2 F protein, both of which were necessary for chimaeric F proteins to prevent induction of cell fusion with the SV-41 HN protein, Consequently, it was proved that a given chimaeric F protein, harbouring regions P1 and P2 together with either of region M1 or M2, induced cell fusion specifically with HN proteins of PIV-2 and MuV, the same as the PIV-2 F protein, Region M2 was located at the membrane proximaI end of the PIV-2 F1 ectodomain, while regions P1, M1 and P2 clustered together in the middle of the ectodomain, These regions on the PIV-2 F protein may be involved in a putative functional interaction with HN proteins, which is considered to be a prerequisite for cell fusion.