Transcripts encoding high molecular weight (Hwt) isoforms of microtubule-associated protein 2 (MAP2) have been localized in the dendritic compartment of neurons. In contrast, nearly all other neuronal messages, including transcripts encoding low molecular weight (Lwt) MAP2 isoforms, are restricted to cell somas. The mechanisms underlying the dendritic localization of Hwt-MAP2 transcripts are not known. In non-neuronal systems, mRNAs, are localized via signal sequences situated in their 3' untranslated regions (3' UTRs). In this study, we have localized the putative dendritic targeting element (DTE) in Hwt-MAP2 mRNAs by comparing the nucleotide sequences of the somatically localized 6 kb Lwt-MAP2 transcripts with the dendritcally localized 9 kb messages. Our analysis shows that both 6 kb and 9 kb transcripts have identical 3' - and 5'- UTRs, precluding the possibility that the DTE lies in these regions. Within the coding region a single segment that is unique to 9 kb Hwt MAP2 transcripts was identified. These findings suggest that the DTE lies within the 4 kb RNA segment that encodes the projection domain of Hwt-MAP2.