Previously we described an embryonic cell surface glycoprotein, ESGp, associated with the t-embryonic lethal alleles of the mouse t complex. This antigen is expressed on the cell surface of both early mouse embryos and embryonal carcinoma (EC) cell lines. The antigen is localized to areas of cell-cell contact in EC lines and redistributes to the outer edges of the blastomeres during compaction, thereby indicating a potential role in embryonic cell-cell interaction. We now report that this t-complex-associated ESGp is homologous to the mouse lysosomal-associated membrane protein-1 (LAMP-1). Limited protein sequence analyses of the amino terminal and an internal peptide indicate considerable homology with the LAMP-1 protein. Biochemical parameters such as protein core size, sulfation and phosphorylation status, and resistance to proteolysis also demonstrate homology. While we detect only a single message with a mouse LAMP-1 cDNA probe via Northern blotting, Southern analyses indicate the existence of at least two homologous LAMP-1 genes. Additionally, we present evidence suggesting that ESGp/LAMP-1 serves as a substrate which may be differentially glycosylated by the activities of the gene products of the different t-lethal alleles.