As part of a study of turnover of rat olfactory receptor neurons we have been examining immunohistochemical expression of members of the 70 kD heat shock protein (HSP70) family in the olfactory epithelium. Expression of HSP70 family members is up-regulated in many cells following exposure to physiologically stressing conditions. Because dying neurons are likely to undergo some sort of physiological stress before the onset of frank degeneration, we hoped that anti-HSP70 monoclonal antibodies would prove to be useful markers for early stages of olfactory neuron cell death. Two anti-human HSP70 monoclonal antibodies were used, Mabs 2A4 and 3a3. Two-dimensional gel electrophoresis/western blot analysis indicates that these Mabs are reactive with the HSC70 and HSP70 members of the rat HSP70 family. Immunohistological observations show that both Mabs are strongly reactive with a widely dispersed subpopulation of olfactory receptor neurons. Morphological, immunohistological, and autoradiographic birthdating analyses demonstrate that reactive cells are fully mature receptor neurons. Their reactivity, however, does not appear to be stress-related. More significantly, axons of reactive neurons show intense anti-2A4 reactivity. This has allowed us to trace these axons to their target glomeruli in the olfactory bulb, demonstrating that the reactive neurons project to just one to two glomeruli on either side of each bulb via consistent and predictable pathways. This is the first subpopulation of olfactory receptor neurons to be traced to such a small number of glomeruli. Given this extremely small number, it seems likely that the reactive receptor cell subpopulation serves some specific olfactory function. In addition, axonal 2A4 reactivity should also prove useful in defining the relative roles of receptor neurons and glomeruli in the establishment of epithelial-glomerular connections.