Oxidative stress caused by poor detoxification efficiency of reactive oxygen species (ROS) may play a role in the development of systemic lupus erythematosus (SLE). Glutathione S-transferase (GST) is involved in the detoxification of ROS and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 are associated with altered enzyme activity. The aim of this study was to determine whether GSTMI (deletion), GSTT1 (deletion) and GSTP1 (Ile(105)-->Val(105)) polymorphisms are associated with susceptibility to SLE or frequency of clinical manifestations according to the ACR diagnostic criteria. DNA was isolated from blood samples collected from 330 patients with SLE and 270 age- and sex-matched controls. GST genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No associations were observed between GSTM1, GSTT1, and GSTP1 genotypes and risk of SLE. Among SLE patients, the GSTM1 null genotype was associated with a lower frequency of hematological disorders (P = 0.012), and a higher SSA(+)/SSB(-) autoantibody profile (P = 0.042). Compared to SLE patients with the GSTT1 non-null genotype, those with the GSTT1 null genotype had a lower frequency of discoid rash (P = 0.018), and nephritis (P = 0.033). Our findings suggest that genetic polymorphisms of GSTM1, GSTT1, and GSTP1 do not influence the risk of SLE, but a deletion of either GSTM1 or GSTT1 may influence certain clinical manifestations of the disease.