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Objective To investigate the association of the absence or presence of aspartic acid at position 57 of the HLA-DQ β chain (NA or A) with susceptibility or resistance to insulin-dependent diabetes mellitus (IDDM) in a South Chinese population.Methods Sixty-nine IDDM patients and 47 healthy controls in a South Chinese population were HLA-DQB1 genotyped by one-step sequence specific polymerase chain reaction (ssPCR).Results The frequencies of NA and A were 64.5% and 35.5% in the IDDM patients, and 40.4% and 59.6% in the control subjects respectively (RR for NA was 2.68, P<0.01). The frequencies of NA/NA, NA/A and A/A phenotypes were 47.8%, 33.3% and 18.8% in the IDDM patients, and 31.9%, 17.0% and 51.1% in the controls respectively (P<0.01). The frequency of A/A phenotype was significantly lower in the IDDM patients than in the control subjects (RR=0.22, P<0.01). DQB1* 0302 and DQB1* 0201 were more frequent in IDDM patients than in control subjects. The younger the age of IDDM onset, the higher the allele frequencies of DQB1* 0201 and DQB1* 0302.Conclusion The present study suggests that the NA confers the susceptibility to IDDM, while the A confers the protection against IDDM in patients of South Chinese origin. These associations are more clearcut in childhood-onset IDDM patients.