Fifty-eight systemic lupus erythematosus (SLE) patients and 59 normal controls of the Han nationality in Hunan province were involved in this study to analyze the correlation between HLA-DR2 group specific amplification in combination with HLA-DRB generic amplification PCR/SSCP technique to detect the sequence variation within exon 2 of HLA-DR2 alleles outside the sequence specific primer matching positions. The results were that HLA-DR2 was strongly correlated with SLE (RR = 2.71, P < 0.01); and HLA-DRB1 * 1501 was the allele correlated with disease (RR = 3.01, Pc < 0.05). In addition, PCR/SSCP showed that there was not any novel sequence variation in exon 2 of HLA-DR2 alleles in the Han nationality in Hunan province.