The association between human leukocyte antigen (HLA) homozygosity and measles antibody levels was assessed in a volunteer group of 242 children. Serum samples were tested for measles IgG antibodies, class I and class II HLA alleles were typed, and associations were examined between HLA homozygosity and antibody levels. Children who were homozygous for at least 1 locus were twice as likely to be seronegative (odds ratio, 1.97; 95% confidence interval, 1.08-3.61). Children who were homozygous at >/=1 loci were increasingly likely to be seronegative (chi(2) test for trend; P=.02). When serum antibody levels were examined as continuous variables, children who were homozygous at certain loci tended to have lower mean antibody levels. These results suggest that lack of HLA diversity may limit the range of peptides that can be presented to antibody-producing cells, potentially resulting in a decreased immune response to viral infections.