The DQw7 allele at the HLA-DQB locus is associated with susceptibility to IgA nephropathy in Caucasians. The frequencies of the MHC class II HLA-DR and DQ alleles in 36 Caucasian patients with IgA nephropathy (IgAN) were analyzed by RFLP analysis and allele specific oligonucleotide (ASO) probing of specifically amplified genomic DNA. The class II alleles HLA-DR4 (52.7%) and DR5 (30.5%) were increased in the patient group compared to 1103 UK Caucasoid controls, but these increases were not statistically significant. However, there was a significant increase in the HLA-DQw7 allele frequency (71%) (c = 27.8%, χ2 = 29.2, P < 0.001, Relative Risk = 6.17). This can be explained by linkage disequilibrium between the DQw7 allele at the DQBl locus and DRB1 genes of some DR4 and all DR5 haplotypes. The polymorphic portion of the DQα chains from DR4, DQw7 and DR5, DQw7 haplotypes differ but they have identical DQβ chains. DNA encoding DQw7 allele at the DQBl locus was sequenced in two patients and was identical to that previously published. We conclude that the DQw7 allele at the DQBl locus is strongly associated with susceptibility to IgAN in Caucasians.