Marked differences in the apparent Mrs of the HN, NP and F proteins of simian virus 5 (SV5) and parainfluenza virus type 2 (PF-2) were revealed by SDS-PAGE. To examine the antigenic relationships between SV5, PF-2 and other paramyxoviruses, monoclonal antibodies (MAbs) specific to PF-2 were isolated. These antibodies had specificities for the HN, NP and P proteins and together with 54 MAbs to SV5 were tested for their ability to react with SV5, PF-2, PF-3, mumps and measles virus proteins. Most of these MAbs (55 out of 60) reacted with homologous virus only. However, five reacted with both SV5 and PF-2. These antibodies had reactivities to the NP, M and P proteins. Furthermore, one of the antibodies with reactivity to the P protein also reacted with mumps virus. Although none of the 21 MAbs with specificities for the HN protein of either SV5 or PF-2 cross-reacted with heterologous virus, some antigenic similarities between the HN protein of SV5 and PF-2 could be detected. This was demonstrated by raising a series of polyclonal antisera to purified preparations of SV5 or PF-2 HN proteins in BALB/c mice, and testing for their ability to neutralize both SV5 and PF-2 and also to immunoprecipitate the HN proteins of these viruses. Surprisingly, while low levels of cross-neutralizing antibody could be detected in some sera (e.g. neutralization of SV5 1:1600 and of PF-2 1:80), other sera with similar neutralization titres against homologous virus failed to neutralize heterologous virus. Furthermore, only a minority of the anti-HN antisera showed any immune-precipitating activity against the heterologous HN protein.