We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.