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 (see Bernardi, 2000. Gene 241, 3 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 that a biased gene distribution towards GC-rich isochores applies to both tissue-specific and housekeeping genes. Moreover, the analyses of recently published data on the distibution of the gene expression levels alonor the chromosomes, and their base composition, further support that highly transcribed genes are localized in GC-rich isochores. Since gene density and transcriptional levels are correlated with each other and both are correlated with the GC level of the isochores, the biased gene distribution in the human genome presumably is the result of selection at the gene expression levels. (C) 2002 Elsevier Science B.V. All rights reserved.