The analysis of 650 HLA-A:HAL-B:Bf three-factor haplotypes revealed significant associations only between alleles of the very closely linked genes HLA-A and HLA-B, and Bf, respectively. Most striking is the highly significnat association of the rare Bf variant F1 with HLA-B18 and of S1 with HLA-B13, HLA-B14, and HLA-Bw21. Only random allele distributions were observed when considering the somewhat more distant genes HLA-A and Bf or the higher order interaction at all three genes. From these findings it seems likely that the linkage disequilibrium within the MHC is not due to selective forces, but rather due to a short evolutionary period.