Allocation of cadaveric donor kidneys in the UK is founded on matching for HLA-A, -B and -DR, primarily at the broad specificity level. Increasing evidence shows that matching at a higher resolution and consideration of additional loci, such as HLA-C, -DQ and -DP, improves graft outcome. The aim of this study was to clarify the typical level of split specificity HLA-A, -B, -C, -DR, -DQ and allelic -DRB1 and -DQB1 mismatching in 'favourably matched' cadaveric renal transplant pairs. Two hundred and thirty-seven cadaveric donor/recipient pairs, 'favourably matched', according to United Kingdom Transplant criteria, were typed at the split specificity level for HLA-A, -B, -C and at the allele level for HLA-DRB1 and -DQB1. The level of split specificity and allele mismatching was then assessed. Overall, 66.7% of the patients had at least one HLA-C mismatch with their donors; 36.9% of those matched for HLA-B and 85.5% of those mismatched for HLA-B (P<0.0001). A broad specificity HLA-A or -B mismatch influenced the presence of an HLA-B, or HLA-A split specificity mismatch, respectively, (P<0.05) but made no significant difference to the presence of an HLA-DR split mismatch. Overall, 4.6% of the patients were mismatched for HLA-DR split specificities but 30.4% were mismatched at HLA-DQ and 50.6% had at least one HLA-DRB1 or -DQB1 allele mismatch. Considerable HLA-A, -B, -C, -DR, -DQ matching heterogeneity exists even amongst 'well matched' renal transplant patient groups. Little is known about the effects of combinations of mismatched specificities on graft survival. Thus, further investigation is merited particularly for HLA-C and -DQ mismatching.