Our laboratory has recently identified a keratan sulfate proteoglycan (KSPG), named claustrin, that inhibits neural cell adhesion and neurite outgrowth in the chick nervous system. Antisera prepared against claustrin were used to screen a cDNA expression library from embryonic day 9 chick brain. Initial characterization of positive cDNAs revealed a high degree of homology to the mouse MAP1B gene, although these cDNAs represent a 5' truncated fragment of MAP1B. Protein sequencing of three peptides derived from a tryptic digest of purified, keratanase-treated claustrin also revealed strong homology to MAP1B, and confirmed the authenticity of the 3.4 kb claustrin cDNA. To further determine the relationship between these two proteins, we used antibodies against MAP1B and KSPGs in immunoblotting and immunohistochemical studies. These studies demonstrated cross-reactivity between MAP1B and claustrin antibodies, and that monoclonal antibodies to cartilage keratan sulfate react with MAP1B in rat nervous tissue, and with claustrin in the chick nervous system. In addition, keratanase treatment of a taxol microtubule fraction from chick or rat brain eliminated MAP1B, as detected by immunoblotting with the MAP5 monoclonal antibody. These results suggest that MAP1B and claustrin are highly related, if not identical, proteins.