Glia-derived nexin (GDN) is a 43 kd cell-secreted protease inhibitor with neurite promoting activity. We have raised specific polyclonal antisera to rat GDN. These antibodies stain a single band at 43 kd on immunoblots of concentrated C6 glioma-conditioned medium and have been used to demonstrate that GDN is present in the olfactory system of the rat. One band at 43 kd is recognized by the GDN antibodies on immunoblots of olfactory bulb homogenate. Immunohistochemistry shows that GDN occurs predominantly in the olfactory nerve layer of the olfactory bulb and in the olfactory submucosa. Comparative studies with antibodies against vimentin, GFAP, and fibronectin suggest that anti-GDN recognizes cells associated with the olfactory system, but not exclusively the olfactory neurons themselves. Data from the immunohistochemical studies were confirmed by RNA blots and GDN mRNA expression throughout development of the olfactory bulb. The high levels of GDN in the rat olfactory system may be related to the continuous degeneration and regeneration phenomena taking place in these structures.