Genes of the MAGE family direct the expression of tumor antigens recognized on a human melanoma by autologous cytolytic T lymphocytes. Twelve closely related MAGE genes are located in the Xq28 region. These genes share 60-98% nucleotide identity in their coding region. The presence of homologous genes in a region of Xp21.3 has been reported previously. We obtained the complete sequence of a 42-kb stretch of this region. It contains four MAGE-related genes, which we propose to name MAGE-B1, B2, B3, and B4 (HGMW-approved symbols MAGEB1, MAGEB2, MAGEB3, and MAGEB4). The coding regions of these genes share 66-81% nucleotide identity and show 45-63% identity with those of the MAGE genes located in Xq28. Like the MAGE genes located in Xq28, the MAGE-B genes are silent in normal tissues with the exception of testis. Like MAGE-1, 2, 3, 4, 6 and 12 (HGMW-approved symbols MAGEA1, 2, 3, 4, 6, and 12), genes MAGE-B1 and MAGE-B2 are expressed in a significant fraction of tumors of various histological types. The transcription of MAGE-B1 and MAGE-B2 can be induced by 5-aza-2'-deoxycytidine, suggesting that the activation of these genes in tumors results from a demethylation process.