The objective of this study was to investigate whether an octamer transcription factor gene (OTF3) located within the MHC region of chromosome 6 is involved in determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish population. An OTF3 HindIII polymorphism was characterized by restriction fragment length polymorphism analysis of polymerase chain reaction amplified genomic DNA in 69 patients with SLE and 60 controls. No differences in the OTF3 allelic or genotypic distribution between healthy controls and patients with SLE were found. In the group of patients with diffuse proliferative glomerulonephritis, where we have previously detected the strongest MHC association, we did not observe OTF3 linkage either. In conclusion, the OTF3 gene does not appear to be associated with SLE in the Spanish population. This might be due to the distance of the gene from the HLA class II-III region where more relevant autoimmune-related genes are located.