Wegener's granulomatosis, an anti-neutrophil cytoplasmic antibody (ANCA)-positive systemic small vessel vasculitide, is characterized by inflammatory lesions with granuloma formation in the upper and lower airways, pauci-immune glomerulonephritis, and anti-proteinase 3 autoantibodies. Although Wegener's granulomatosis is considered idiopathic, there has been substantial interest in environmental factors as either etiologic or accelerating risk factors, with Staphylococcus aureus having attracted substantial attention as one such environmental factor. Although consensus about etiology remains elusive, the nature of the host response has emerged as an important determinant for disease phenotype and severity. Although Wegener's granulomatosis occurs sporadically, and does not show classical familial clustering and transmission characteristic of some autoimmune diseases, the identification of important genetic factors in Wegener's granulomatosis is not only feasible but also potentially very fruitful in providing insights into pathogenesis and potential therapeutic targets. Building on the clinical trial of etanercept in Wegener's granulomatosis, Dr. Edberg, in collaboration with Drs. Kimberly and Kaslow, is developing a renewable genetic repository to explore the relationship between the Wegener's granulomatosis diathesis and genetic polymorphisms in candidate molecules, selected for their role in pathophysiology. These studies also will involve identification of new polymorphisms in such molecules and application of these to this cohort.