Insulin-dependent diabetes mellitus (IDDM) is strongly associated with the presence of arginine in position 52 of the DQ alpha chain and absence of aspartic acid in position 57 of the DQ beta chain in Caucasians. With the aim of confirming this association in Chinese, extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes was studied using samples from 48 IDDM patients and 46 healthy nondiabetic control subjects. Three major findings emerged from our analysis. 1) DQ alpha 52-Arg and DQ beta 57-non-Asp are strongly associated with IDDM susceptibility as compared with controls (P < 0.001 and 0.005, respectively). 2) DQ beta 57-non-Asp homozygous (NA/NA) is associated with increased susceptibility to IDDM (22.9% vs 2.2% in controls, P < 0.01). DQ beta 57-Asp homozygous (A/A) is associated with protection against IDDM (14.6% vs 47.8% in controls, P < 0.01). 3) In this study, about 14.6% of IDDM patients were homozygous for DQ beta 57-Asp, compared with 0% of American patients. Only 22.9% were homozygous for DQ beta 57-Asp, compared with 96% of American diabetic subjects in a previous study. Thus it is unlikely that the DQ beta 57 amino acid has a major effect on IDDM susceptibility in Chinese.