In the immune system, mCD24, the mouse homolog of the human glycosyl phosphatidylinositol-anchored glycoprotein CD24, may play a role in cell adhesion. In the nervous system, the function of mCD24 has not been determined, but its transient expression by neurons suggests that it may be involved in axon growth in development. Here we show that retinal ganglion cells (RGCs) and dorsal root ganglion (DRG) neurons express mCD24 in the developing but not adult mouse in vivo and in DRG neurons of the injured adult peripheral nervous system (PNS). In vitro, mCD24 was expressed by immature neurons and by a subpopulation of adult DRG neurons. To analyze the possible function of mCD24 in the nervous system, we prepared rat C6 glioma cells stably transfected or retrovirally infected with mCD24 cDNA. The cells did not exhibit changes in their adhesive properties or cell division rate after transfection or infection. When mCD24-expressing cells were used as monolayer substrates for culturing RGCs and DRG neurons, neurite outgrowth was inhibited, depending on neuronal age and on the relative levels of mCD24 in the monolayer. This inhibition, however, was not dependent on the expression of mCD24 by the neurons themselves, because DRG neurons of a mouse deleted of the mCD24 gene showed the same response. These results show that mCD24 interacts in a heterophilic manner with a developmentally regulated molecule expressed by neurons, and they suggest that in vivo, mCD24 may inhibit the further extension or collateral branching of axons in late embryonic development.