Abstract Genes are non-uniformly distributed in the human genome, reaching the highest concentration in GC-rich isochores. This is one of the fundamental aspects of the human genome organization (Gene 241/259 (2000a,b) 3/31, for a review). In the present paper the gene distribution was analyzed in relationship to the gene expression pattern and levels. In this study evidence is produced showing: (i) that a biased gene distribution towards GC-rich isochores applies to both tissue-specific and housekeeping genes; and (ii) that genes localized in GC-rich isochores have high transcriptional levels. Since gene density and transcriptional levels are correlated with each other and both are correlated with the GC content of the isochores, the biased gene distribution in the human genome presumably is the result of selection at the gene expression levels.