Genetic variation in immunoglobulin γ (GM) and ĸ (KM) chains was associated with systemic lupus erythematosus (SLE) in some studies. However, the data are conflicting, and only one study examined associations in African-Americans. We examined GM and KM allotypes, by race, in a population-based case-control study of SLE. Sera from patients (n = 222) and controls (n = 273) were typed for GM and KM allotypes by a hemagglutination inhibition method. GM phenotypes were not significantly associated with SLE in African-Americans or Caucasians. However, the frequency of KM phenotypes in Caucasian patients was significantly different from that in controls (p = 0.032). KM3,3 was associated with an increased risk, whereas KM1,3 was associated with a lower relative risk of SLE. In African-Americans, however, the pattern of associations with KM phenotypes differed from that in Caucasians, and the overall difference between patients and controls was not statistically significant.