OBJECTIVE: To estimate the annual incidence of systemic lupus erythematosus (SLE) over a 10-year period in the UK, and to examine age-, sex-, and region-specific rates. METHODS: The study was based on the UK General Practice Research Database (GPRD), which covers approximately 5% of the UK population. We estimated SLE incidence rates, during the period 1990-1999, among persons registered with practices contributing to the GPRD, representing >33 million person-years of observation. RESULTS: A total of 1,638 patients with incident SLE (1,374 females, 264 males) were identified. The age-standardized SLE incidence in the UK during the 1990s was 7.89 per 100,000 (95% confidence interval [95% CI] 7.46, 8.31) for females and 1.53 per 100,000 (95% CI 1.34, 1.71) for males (overall female-to-male ratio 5.2:1). Peak incidence occurred at age 50-54 years for females and 70-74 years for males. There was a small but insignificant increase of SLE incidence over the 10 years among females but not males. No clear association between latitude and SLE incidence was found, but regional variations existed, with age-standardized rates ranging from 3.56 per 100,000 (95% CI 3.00, 4.13) for the West Midlands to 7.62 per 100,000 (95% CI 5.59, 9.65) for Northern Ireland. CONCLUSION: This study provides updated estimates of SLE incidence in the UK. Standard methodology throughout the study period and target population allowed for comparison of rates over time and across regions.