The role of X-chromosomal genes in spermatogenesis has been subject to a number of studies in different organisms. Recently, it was proposed that the X chromosome has a predominant role in premeiotic stages of mammalian spermatogenesis. We analyzed the expression of a representative set of 17 X-linked and 48 autosomal germline-restricted genes in different stages of human germ cell development. In accordance with data from other species, we show that the human X chromosome is indeed significantly enriched for genes activated in premeiotic stages of spermatogenesis. In contrast to recent studies, however, we found that expression of these genes is not restricted to spermatogenesis, but is activated in oogenesis as well. Furthermore, we show that activation of this subset of genes merely depends on demethylation of their promoter regions. Moreover, our data suggest that genes activated in premeiotic stages of gametogenesis are sex-indifferent and are regulated by DNA methylation. Gene activation patterns involved in spermatocyte-specific differentiation, in contrast, appear to be initiated not before entry into meiosis and underlie a more complex regulation, presumably involving specific transcription factors and/or chromatin remodeling mechanisms.