The purpose of this study is to describe the clinical presentation and natural history of pauci-immune renal vasculitis and determine whether particular presenting features or administered therapies predict outcome. We reviewed our experience since 1984 with such vasculitides, and 94 cases of pauci-immune vasculitis were identified. Presenting features were as follows: men, 63%; mean age at biopsy, 59 years; and mean serum creatinine level, 5.0 mg/dL. Patients with no extrarenal involvement had a tendency to present with a greater serum creatinine level. Since the antineutrophil cytoplasmic autoantibody (ANCA) assay became available, 77% of the patients tested were ANCA positive. In terms of natural history, 27 patients required dialysis immediately, there were 22 renal relapses, 28 patients progressed to dialysis, 10 patients died before requiring dialysis, 19 patients were lost to follow-up, and 37 patients remain active, not on dialysis. Overall, half the patients recovered some renal function, one third remained stable, and one sixth deteriorated. Female sex and angiotensin-converting enzyme inhibitor use predicted favorable outcome (P < 0.05). Advanced age, male sex, respiratory tract involvement, and a greater relapse rate predicted unfavorable outcome (P < 0.05). The incidence of pauci-immune renal vasculitis appears to be increasing, likely related to the emergence of the ANCA assay. Attempts to classify patients based on existing schemes may result in delayed diagnosis and therapy, with subsequent poorer outcomes. Also, given the increased mortality of patients with respiratory tract involvement, we speculate that respiratory tract disease therapeutic and monitoring regimens are ineffective. In general, we conclude that pauci-immune renal vasculitis is a heterogeneous disorder with an unfavorable prognosis.