MAP2 proteins are among the major microtubule-associated proteins in the vertebrate nervous system. The high molecular weight proteins MAP2a, MAP2b and the low molecular weight protein MAP2c are encoded by distinct mRNAs generated by alternative splicing from the same primary transcript. MAP2c is primarily found in embryonic and neonatal brain. Using primers selected in the 5' and 3' non-coding regions of the rat MAP2c sequence and reverse transcription-coupled PCR from adult rat brain RNA, we have amplified and sequenced the entire coding region of a novel MAP2 isoform containing a 93 base pair insertion. Sequence analysis reveals that the additional exon encodes a domain that is highly homologous to repeats found in the 3' end of the coding region of MAP2, MAP4 and Tau mRNA sequences. In these microtubule-associated proteins, the domains encoded by the repeats are involved in microtubule binding and bundling.