A set of 87 multicase families with systemic lupus erythemathosus (SLE) from European (Iceland, Sweden, England, Norway, Italy, and Greece) and recently admixed (Mexico, Colombia, and the United States) populations were genotyped and analyzed for 62 microsatellite markers on chromosome 1. By parametric two-point linkage analysis, six regions (1p36, 1p21, 1q23, 1q25, 1q31, and 1q43) were identified that have LOD scores of Z>or=1.50, with different contributions, depending on the population of origin of the families (European or admixed American). All of the regions have been described previously and have therefore been confirmed in this analysis. The locus at 1q31 showed a significant three-point LOD score of Z=3.79 and was contributed by families from all populations, with several markers and under the same parametric model. Analysis of a known mutation in the CD45 gene did not support the role that this mutation plays in disease. We conclude that the locus at 1q31 contains a major susceptibility gene, important to SLE in general populations.