Olfactory marker protein (OMP) is a phylogenetically conserved, 19-kDa, acidic, soluble protein found abundantly in mature olfactory sensory neurons. Its function has been enigmatic although recent evidence from studies on OMP null mice suggests that neurons lacking OMP exhibit altered physiological activity, including prolonged onset and recovery kinetics following stimulation.(2) We have reported increased expression of OMP in individual surviving sensory neurons that have been deprived of their target, the olfactory bulb.(3) Because olfactory epithelia deprived of their target also exhibit an increased rate of cell division we investigated the effect of recombinant OMP on cell division in organotypic cultures of fetal rat (embryonic day 19) epithelium grown for 3 days in vitro, After 3 days, cultures were given a 1-hr pulse of a mitotic marker, bromodeoxyuridine (BrdU), fixed and prepared for inmunohistochemistry to determine the number of proliferating cells. We found a dose-dependent increase in the number of BrdU-positive cells/100-mm length of epithelium. The number of labeled cells increased incrementally, reached a plateau at 25 pM OMP/ml culture medium, 50% higher than in cultures with no OMP added, and remained at that level at 50 and 100 pM doses. Controls included trypsinized OMP and addition of equivalent volumes of TRIS buffer lacking OMP, These results, taken together with previous studies on several growth factors' indicate that regulation of neurogenesis in olfactory tissue is a multifactorial process and that OMP may play a role.