The observed number of alleles (na) at some human major histocompatibility complex (HLA)loci is more than twice as large as the pairwise mean number (k̄B) of nonsynonymous nucleotide substitutions in the peptide-binding region (PBR), although the k̄B is about the same as that predicted by a model of balancing selection. In order to assess the joint effect of intra-locus recombination and balancing selection on the HLA polymorphism, large scale computer simulation is conducted. It reveals that (1) both rate and location of break points of recombination are crucial factors to determine na, (2) intra-locus recombination tends to decrease k̄B, and (3) the rate of PBR nonsynonymous substitutions is insensitive to the recombination rate. Although a large number of alleles can be generated by intra-locus recombination, this fact alone is insufficient to account for the HLA polymorphism. It is argued that even patchwork patterns of PBR motifs, presumably owing to intra-locus recombination, must be maintained primarily by balancing selection.