Objective. The Gullah population of the Sea Islands of South Carolina is a unique group of African Americans who, due to geographic and cultural factors, remained isolated with minimal genetic admixture until the 1950s. Because of the unique homogeneous nature of the Gullah, we sought to define the genetic and environmental factors contributing to systemic lupus erythematosus (SLE) in this population.Methods. Using data from our ongoing cohort study of lupus in the Gullah population, which we established in 2003, disease characteristics and serologic profiles were summarized for 184 patients with SLE, 144 unaffected first-degree relatives, and 144 matched unrelated, unaffected control subjects. These findings were compared with those in 2 other large cohorts of African Americans with SLE.Results. In the Gullah cohort, we observed a high prevalence of SLE multiplex families (26.6%), malar rash (56.0%), discoid rash (34.2%), photosensitivity (60.9%), and oral/nasal ulcerations (43.5%), but a lower prevalence of hematologic and pleuropericardial disease than has been reported in other African American cohorts. Overall renal and central nervous system involvement, number of American College of Rheumatology disease criteria met, and SLE Damage Index scores were similar to those reported in other cohorts. Of interest, male and female first-degree relatives and male and female control subjects in this cohort had similar rates of antinuclear antibody positivity, whereas lupusspecific antibodies were more prevalent in the women than in the men.Conclusion. These data indicate that the severity of lupus in the Gullah population is similar to that in other African American populations, whereas skin disease and familial disease prevalence are increased in the Gullah. These findings suggest that there is an increased genetic influence on overall disease in this cohort compared with that in other African American cohorts, which confirms the unique nature of this cohort.African Americans have a 3-fold increased prevalence of systemic lupus erythematosus (SLE), develop SLE at an earlier age, and have increased SLE-related morbidity and mortality compared with Caucasians (1-5). Multiple factors, including genetic, environmental, and socioeconomic factors, likely underlie the ethnic disparity in SLE. Socioeconomic and genetic differences alone, however, cannot explain the significant increase in prevalence of SLE in the last 20 years or the gradient of SLE between West Africa, where it is a rare disease (6-9), and the United States, where it is prevalent. These latter findings suggest that environmental factors play a key role in inducing lupus and influencing disease severity.