The extracellular haemoflagellate Trypanosoma brucei brucei releases a factor, which can induce CD8+ T-cells to produce interferon-gamma. Interferon-gamma derived from these cells promotes proliferation of the trypanosomes. We now report that these trypanosomes can interact with small neurons in cultures of rat dorsal root ganglia, which contain an interferon-gamma like immunoreactive molecule. Cultures of dorsal root ganglia were able to promote the proliferation and survival of the trypanosomes and this growth promoting effect was blocked by monoclonal antibodies against the trypanosome-derived lymphocyte triggering factor, interferon-gamma and CD8+ and by Fab-fragments of these antibodies. Living trypanosomes and the factor induced an increase in expression of major histocompatibility complex class I antigens in the cultures; this induction was blocked by Fab fragments of the interferon-gamma antibody, indicating that it is mediated by release of the neuronal interferon-gamma-like immunoreactive molecule. These data suggest, that the interferon-gamma-like immunoreactive molecule in small dorsal root ganglion neurons mimics certain physiological effects of lymphocyte derived interferon-gamma. Furthermore, the trypanosomes and small sensory neurons seem to interact bidirectionally by release of the trypanosome-derived lymphocyte triggering factor and the neuronally derived interferon-gamma-like molecule, whereby, perhaps, neuronal disturbances may be elicited and trypanosome proliferation regulated.