Using fluorescent in situ suppression hybridization to metaphase chromosomes, we have directly shown that CpG islands are predominantly found in the early replicating (R band) regions of the genome. Conversely, late replicating (G band) DNA is sparsely populated with islands. The very highest concentration of CpG islands is in a subset of R bands, most of which are known as T bands. We suggest that there is an interdependence between the differences in island density and the behaviour of chromosomal domains. Our findings indicate which regions of the genome will yield the highest density of coding sequence information. An awareness of local island density may influence the choice of method for identifying exons in genomic DNA.