Linkage disequilibrIum (LD), the association of alleles at different loci, is a powerful tool for genetic mapping and for investigating, at the population level, processes such as recombination, selection, mutation and admixture. Little is known about the distribution of LD across mammalian genomes. Therefore, a survey was undertaken, using microsatellite loci, to evaluate the distribution of LD over several regions of human chromosome 4. Radiation hybrid (RH) and linkage maps provided information on physical and genetic distances between these lad. A Finnish popu lation sample was genotyped using 32 mlcrosateilite lad, and partial marker haplotypes were determined. Assessment of LD was performed, between all pairs of iocl, using the Fisher's exact test. LD was detected between several loci that were separated by more than 1 Mb or 1 cM. Detection of LD was strongly associated with small physical distance; its relation to genetic distance was more equivocal. This result may support the hypothesis that linkage maps are relatively inaccurate over small distances. Our results suggest that LD is widely distributed in anonymous regions of the human genome and its use may allow more accurate measurement of small genetic distances than does standard linkage analysis. Alternative explanations are considered for comparisons in which LD is not detected between tightly linked loci.