HLA-A/B haplotype frequencies were estimated in a sample of 2355 bone marrow donors born in a subregion of Tuscany (Italy), and the HLA-A, -B, -DR haplotype frequencies were estimated in a subset of 809 individuals. This area was divided in 10 subsamples (two-locus haplotypes), or six subsamples (three-locus haplotypes), all with sample size >50, based on administrative boundaries. A considerable level of heterogeneity of haplotype frequency was present among subsamples; this heterogeneity was associated to a large variation (up to 4-fold) of the number of new donors that must be typed in order to reach 50% chance of finding an HLA-A, -B phenotype of intermediate frequency. Knowledge of the genetic structure of the population at a microgeographic level may be useful in directing the search of specific bone marrow donors.