Several groups have previously shown that the T-cell receptor (TCR) constant-beta (C beta) chain locus is associated with susceptibility to Type 1 diabetes, although other studies have failed to show this. We have extended these studies by investigating 125 individuals with Type 1 diabetes and failed to confirm the significantly increased frequency of the 10;9.2 kb TCR-C beta/Bgl-II genotype in our patient population. However, further analysis showed that the 10;9.2 kb TCR-C beta genotype was significantly increased in those patients with no microvascular complications after 20 years of diabetes compared to those patients with complications (proteinuria, overt neuropathy, and moderate or severe retinopathy) 69.2% vs 31.7%, respectively, p < 0.005 Pc = 0.025). Similar results were also found in a second group of 74 patients who were analysed in the same way. Hence, the failure of some investigators to confirm the association between TCR-C beta and Type I diabetes may be due to heterogeneity in the patient populations being studied.