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OBJECTIVE: To investigate the frequency, distribution, and mortality of systemic lupus erythematosus (SLE) in a defined area of northwest Greece. METHODS: Cases were recorded from 3 sources: inpatients and outpatients referred to the rheumatology clinic of the Ioannina University Hospital; inpatients and outpatients referred to the rheumatology clinic of Ioannina General Hospital; and patients referred to private rheumatologists practicing in the study area. All patients identified between January 1, 1982, and December 31, 2001, resident in the study area were included. Diagnosis was confirmed by the 1982 revised criteria of the American College of Rheumatology. Incidence and prevalence rates were calculated as number of cases per hundred thousand inhabitants. Population data were based on the 1981, 1991, and 2001 National Census. RESULTS: A total of 178 cases of SLE were diagnosed during the study period, giving a mean annual incidence rate of 1.9 cases/100,000 inhabitants (95% CI 1.49-2.31). The female/male ratio was 7.4. A significant variation of SLE rates among different districts of the study area was observed. Incidence rates were higher for the urban population. The peak of incidence was observed in the 30-49 age group for both sexes. There was a slight increase in the incidence of SLE during the study period. The 5 year survival rate was 96.8% and the 10 year survival rate was 90.3%. CONCLUSION: We found a relatively low frequency of SLE in northwest Greece. Age at diagnosis was younger than expected.