A family with a fragile site on chromosome 6 at band p23 was examined for recombination between the fragile site and HLA. Recombination was observed in four of the 20 offspring in whom it could occur. The estimate of the genetic length of chromosome between the fragile site and HLA is 20 centimorgans (cM) with a lower 95% probability limit of 8.5 cM, placing HLA proximal to the midpoint of 6p22. The most likely regional localization is at 6p21.3, which agrees closely with methods that do not involve recombination with the fragile site. This fragile site does not measurably disrupt recombination frequency, and the allele predisposing to expression of the fragile site is situated at the fragile site.