The transporter associated with antigen processing (TAP) gene products transport peptides from the cytosol to the endoplasmic reticulum for processing by the immune system. We hypothesized that polymorphisms within the TAP genes may influence measles vaccine antigen processing and hence antibody response. TAP genotypes were determined for subjects who were measles vaccine nonresponders (n = 32) and hyper-responders (n = 28). TAP1 and TAP2 alleles were determined by PCR amplification of specific alleles (PASA). Measles vaccine nonresponders were more likely to be homozygous at TAP2 position 665 than were hyper-responders (OR = 5.0, P = 0.016). Lastly, a trend was found in the overall distribution of all TAP2 genotype frequencies between hyper-responders and nonresponders (P = 0.08). No association was found between TAP1 polymorphisms and vaccine response. These data reveal an association between TAP2 genotype and measles vaccine antibody response which may explain one mechanism behind vaccine failure.