Monoclonal antibody (MAb) 8-1H defines a highly conserved ocular melanoma-associated antigen. Based on a potential binding site of MAb8-1, we identified, molecularly cloned, and sequenced the gene, encoding this melanoma-associated antigen from a uveal melanoma copy DNA library. Nucleotide sequence analysis of the melanoma-associated antigen revealed characteristics of a membrane-bound protein of 238 amino acids (approximately 25 kd) with four transmembrane domains. The sequence of the ocular melanoma-associated antigen is identical to the sequence of a recently reported cutaneous melanoma-associated antigen, substantiating our previous studies regarding common antigens between ocular and cutaneous melanoma. In addition, the melanoma-associated antigen shares sequence homology with a number of transmembrane proteins that appear to be involved in growth regulation. The implication of the biological function of this ocular melanoma-associated antigen, its relevance to the malignant phenotype, and clinical applications of the molecular characterization of this melanoma-associated antigen are described.