The human genome is described in the literature as being composed of the isochores, i.e., long (hundreds of kilobases) segments with a homogeneous (G + C) content. We calculated the (G + C) content variations along the DNA molecules of the human chromosomes 21 and 22 and found the variations to be higher everywhere compared to the randomized sequences. Hence the (G + C) content is certainly not homogeneous on the isochore scale in the two human chromosomes. In MATERIALS AND METHODS addition, we found no significant difference between the two human molecules and the genome of E, coli regarding the (G: + C) content variations. Hence no isochores are either present in the DNA molecules of the human chromosomes 21 and 22, or the isochores are also present in the genome of Escherichia coli. In any case, the present communication demonstrates that the isochores should be defined in unambiguous molecular terms if they are to be used for an up-to-date genome structure characterization.