Immunohistochemistry by using monoclonal antibodies named A5 and B2, which specifically recognize cell surface proteins the neuropilin and the plexin, respectively, revealed that olfactory axons in Xenopus tadpoles were classified into several subgroups by virtue of the expression levels of these two cell surface molecules. The vomeronasal axons expressed the plexin but not the neuropilin. The plexin-positive and neuropilin-negative vomeronasal axons form a discrete fiber bundle, even after they joined with the principal olfactory axons. However, the principal olfactory axons were divided into at least two subclasses; the neuropilin-predominant axons which expressed high levels of the neuropilin and low levels of the plexin, and the plexin-predominant axons which expressed high levels of the plexin and low levels of the neuropilin. Within the olfactory nerve the pathways for these two principal olfactory axon subclasses were initially intermingled with each other, but were gradually segregated throughout their courses from the nose to the cerebrum. Eventually, the neuropilin-predominant and the plexin-predominant principal olfactory axon subclasses projected to specified glomeruli in topographically related regions within the main olfactory bulb. Neuroanatomical tracings of the olfactory projection also confirmed the gradual segregation of the pathways for the principal olfactory axons. These results allow us to speculate that both the neuropilin and the plexin are involved in axon interactions, and play roles in the organization of the precise patterns of the olfactory pathway and projection.