This report describes our attempt to establish an experimental animal model for human parainfluenza virus type 4A (HPIV-4A) and 4B (HPIV-4B) infection, which was used to study the immune response to the viruses. Monkeys were inoculated intranasally with the viruses, and at 10 weeks post-infection they were re-infected with homologous subtype viruses. Virus-specific IgM and IgG serum antibodies were measured by ELISA. A small peak of IgM antibody was detected in the monkeys re-infected with HPIV-4B, whereas this response was not detected after re-infection with HPIV-4A. Virus-specific IgA and IgE antibodies were not detected in sera following infection and re-infection with HPIV-4. However virus-specific IgA and IgE antibodies were found in the saliva and nasal exudates of monkeys infected with either HPIV-4A or -4B. Re-infection of monkeys with HPIV-4B also stimulated an IgA and IgE response. To our knowledge this is the first description of an experimental animal. The kinetics of haemagglutinin-inhibition and neutralization (NT) antibodies were similar to that of virus-specific IgG antibodies. The NT titres of sera from HPIV-4A-infected monkeys were enhanced by the addition of complement, whereas complement did not affect the NT activity of sera obtained from HPIV-4B-infected animals. Antigenic specificities of IgG antibody induced by HPIV-4 infection were analysed with radioimmunoprecipitation followed by SDS-PAGE. Anti-NP, -HN and -F antibodies appeared 2 weeks after infection, and the highest titres were found 2 weeks after re-infection. Anti-F antibody production followed a biphasic pattern previously observed in mumps virus infection.