Objective. To examine health disparities as a function of ethnicity using data from LUpus in Minorities, NAture versus nurture (LUMINA), a longitudinal study of patients with systemic lupus erythematosus (SLE); to build an explanatory model of how ethnic disparities occur in this setting; and to suggest appropriate interventions. Methods. LUMINA patients (meeting American College of Rheumatology criteria for SLE) ages ≥16 years of African American, Hispanic (from Texas), Hispanic (from Puerto Rico), or Caucasian ethnicity were studied. In addition to examining the basic features of the cohort, we examined, by univariable and multivariable analyses, the factors associated with disease activity, damage accrual, lupus nephritis, and mortality. An empiric model based on the data presented (and the literature reviewed) was derived to explain the disparities observed. Results. There were substantial differences in the socioeconomic/demographic, clinical, and genetic features among patients from the different ethnic groups, with Texan Hispanic and African American patients exhibiting overall a lower socioeconomic status, different genetic associations, more serious disease at a younger age, and worse intermediate and final outcomes than the Caucasian and Puerto Rican Hispanic patients. A model of disease outcome as a function of the disparities observed was created. Conclusion. Ethnic disparities occur in SLE. Environmental, socioeconomic/ demographic, psychosocial, genetic, and clinical factors play an important role as determinants of the ethnic differences observed. Measures aimed at eliminating these disparities are suggested while further research is conducted to elucidate the basis of these disparities and their changes at the societal level and to eliminate the gap between the rich and the poor. © 2007, American College of Rheumatology.