To evaluate the association of human leukocyte antigen (HLA)-DRB1 alleles with systemic lupus erythematosus (SLE) and lupus nephritis (LN) in the Taiwanese population, and to investigate the possible association of HLA-DRB1 alleles with disease severity in LN. HLA-DRB1 alleles were studied in 105 SLE patients (82 patients with LN, 23 patients without LN) and 855 healthy controls by polymerase chain reaction and sequence-based typing assays. The frequency of the HLA class II alleles DRB1*0301 (Odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.31-3.10, Pc = 0.02) and DRB1*1501 (OR = 2.06, 95% CI = 1.36-3.13, Pc = 0.01) were both increased in SLE patients, compared to healthy controls. The frequency of DRB1*1202 was significantly lower in LN patients than in SLE patients without nephritis (OR = 0.23, 95% CI = 0.09-0.57, Pc = 0.01). No specific allele was significantly associated with an increased or decreased risk for severity of LN in this sample. In Taiwanese people, the DRB1*0301 and DRB1*1501 alleles are significant risk factors for SLE, while the DRB1*1202 allele is protective for LN.