The primary structure of the major embryonic Notch transcript is presented, as determined by sequence analysis of overlapping cDNA clones. The 10,148 bp sequence corresponding to this transcript possesses an 8109 bp open reading frame that potentially codes for a 2703 amino acid protein. We show that this polypeptide contains a repeated structure composed of 36 tandemly arranged 40 amino acid long repeats, which show homology to the epidermal growth factor and other proteins containing EGF-like repeats. Hydropathy plots suggest that the putative Notch protein may span the membrane. We relate these findings to the developmental action of Notch and speculate that the locus may be involved in a cell-cell interaction mechanism that is essential for the differentiation of the ectoderm into neural and epidermal precursors.