Olfactory sensory neurons are replaced throughout the life of vertebrates by proliferation of basal cells and differentiation of the new cells into neurons. Removal of their target, the olfactory bulb, increases proliferation twofold because sensory neurons die prematurely, suggesting that the olfactory bulb provides a trophic substance required for survival. We asked whether mitral cells, a major postsynaptic target of olfactory sensory neurons, are involved in their survival. We report here that depletion of mitral cells increases proliferation and cell death in the olfactory sensory neuron population. Mitral cell loss was induced unilaterally by transection of their axons in the lateral olfactory tract in 18-day-old rats. At all time points after surgery (3 weeks, 7 weeks, 3 months, 14 months) there was a 29% mean reduction in the number of mitral cells ipsilateral to the transection. The surviving mitral cells were smaller than controls and had less rough endoplasmic reticulum. In the olfactory epithelium, proliferation density (BrdU-positive cells/mm epithelial length) in the progenitor basal cells was increased by an average of 20-25% at all time points, as was the number of TUNEL-positive dying cells. The results are consistent with the notion that mitral cells, or the synaptic sites on them, are a source of trophic factor required for maintenance of the lives of olfactory sensory cells. The target field of postsynaptic neurons remaining after lateral olfactory tract transection is insufficient to maintain normal survival of all existing olfactory neurons. In unperturbed animals the proliferation density declines in an age-dependent manner and interestingly the decline on the tractotomized side is parallel. This suggests that with age the sensory cells are less dependent on their targets.