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OBJECTIVE: To clarify which racial differences in disease manifestations can be attributed to differences in other factors such as gender, education, disease classification, and disease duration. METHODS: The study included white and black patients with systemic sclerosis (SSc) treated at a university hospital rheumatology clinic between November 1997 and April 2003. Demographic, clinical, and immunological measurements were obtained on each subject. Using multivariable statistical techniques we assessed differences in disease manifestations between white and black patients after adjusting for gender and classification and duration of disease. RESULTS: Two hundred sixty-three patients (199 whites, 64 blacks) were enrolled in the study. Blacks experienced an earlier age at disease onset than whites and were significantly more likely to have diffuse disease, digital ulcers, digital pitting, impaired lung function, and anti-RNP, and anti-Ro antibodies. Whites were significantly more likely to have anti-centromere antibodies. CONCLUSION: After adjusting for gender, disease classification, and disease duration, whites and blacks with SSc differ in some clinical and immunological manifestations of disease. Whether these differences can be attributed to genetic or environmental factors remains unknown.