Major histocompatibility complex (MHC) alleles have been recognized as genetic factors for developing systemic lupus erythematosus (SLE). In the present study we analyzed whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to develop SLE in a Mexican Mestizo population. A HSP70-2 Pst I polymorphism was detected by a restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) in 107 SLE patients and 158 healthy controls. No statistically significant differences were observed in the HSP70-2 allele distribution between patients and healthy controls. HLA-DR analysis showed an increased frequency of HLA-DR3 allele in the patients group (P Ͻ 0.05, OR = 2.26, EF = 6.0%). On the other hand, when we analyzed HSP70-2 polymorphism in relation to HLA-DR3 allele, we could only detect an increased frequency of AB genotype in the DR3 negative patients (pC Ͻ 0.05, RR = 2.6, EF = 11.3%). Linkage disequilibrium was observed for three haplotypes: HLA-DR3- HSP70