We have found that a 15 kDa protein (p15) produced by a fungus of Helicosporium genus induced characteristic morphological changes on neurites extending from rat cerebral cortex neurons in culture. In the presence of p15, neurite elongation from cortical neurons was markedly inhibited, and they extended short, slender, and less branched neurites. Laminin-induced promotion of neurite outgrowth was also dramatically suppressed. In contrast, p15 promoted nerve growth factor (NGF)-induced neurite outgrowth from PC12 cells, although treatment of cells with p15 alone had little effect. Partial amino acid sequence analysis of p15 revealed that it had limited homology to plant lectins. These results suggest that the mechanism of neurite outgrowth was considerably different between cortical neurons and PC12 cells and that p15 modulated neurite outgrowth in cell type-specific manners.