Interferon-gamma-like immunoreactivity was observed in a subpopulation of 16-day-old embryonic rat spinal ganglion neurons using two monoclonal antibodies directed against different epitopes of recombinant interferon-gamma. During ontogenesis both in vivo and in vitro, it was found that the strong immunoreactivity was confined to small neurons when neurons become morphologically distinct on the basis of size. In vivo, the interferon-gamma-immunoreactive neurons started to express major histocompatibility complex class I antigens after the first postnatal week, while in vitro no such antigen could be detected. A quantitative Elisa method was developed to determine the levels of major histocompatibility complex class I and interferon-gamma in vitro, whereby increased amounts of major histocompatibility complex class I antigen was detected after exposing the cultures to recombinant interferon-gamma and Sendai virus. Sendai virus also caused a small increase in interferon-gamma with a peak about 12 hours after infection. The in vitro system will be used to study further the role of the putative neuronal interferon-gamma-like molecule in the regulation of cell growth, for induction of major histocompatibility complex antigens and in virus infection of sensory neurons.