We have examined expression during spermatogenesis in the mouse of three Y-linked genes, 11 X-linked genes and 22 autosomal genes, all previously shown to be germ-cell-specific and expressed in premeiotic spermatogonia, plus another 21 germ-cell-specific autosomal genes that initiate expression in meiotic spermatocytes. Our data demonstrate that, like sex-linked housekeeping genes, germ-cell-specific sex-linked genes are subject to meiotic sex-chromosome inactivation (MSCI). Although all the sex-linked genes we investigated underwent MSCI, 14 of the 22 autosomal genes expressed in spermatogonia showed no decrease in expression in meiotic spermatocytes. This along with our observation that an additional 21 germ-cell-specific autosomal genes initiate or significantly up-regulate expression in spermatocytes confirms that MSCI is indeed a sex-chromosome-specific effect. Our results further demonstrate that the chromosome-wide repression imposed by MSCI is limited to meiotic spermatocytes and that postmeiotic expression of sex-linked genes is variable. Thus, 13 of the 14 sex-linked genes we examined showed some degree of postmeiotic reactivation. The extent of postmeiotic reactivation of germ-cell-specific X-linked genes did not correlate with proximity to the X inactivation center or the Xist gene locus. The implications of these findings are discussed with respect to differential gene regulation and the function of MSCI during spermatogenesis, including epigenetic programming of the future paternal genome during spermatogenesis.