BACKGROUND Few data are available about the very long-term outcome of patients with proliferative lupus nephritis. METHODS Ninety-three Italian patients with biopsy-proven proliferative lupus nephritis (15 with class III, 9 with class III+V, 64 with class IV and 5 with class IV+V) followed for a median follow-up of 15 years in a single renal unit were considered for this observational study. Patients were treated with an induction treatment consisting of high doses of corticosteroids plus immunosuppressive agents in the more severe cases. This treatment was repeated in the event of a renal flare. Then corticosteroids and immunosuppressive agents were reduced to the minimal effective dose for maintenance. RESULTS Renal survival including death was 97% at 10 years and 82% at 20 years. At the last follow-up visit, 59 patients were in complete renal remission, 18 were in partial renal remission, four patients had chronic renal insufficiency, six had entered end-stage renal disease and six patients had died. At multivariate analysis the lack of achievement of complete renal remission and the occurrence of nephritic flares were significantly correlated both with the risk of doubling plasma creatinine and death or dialysis. Those patients who entered complete renal remission had significantly less probability of developing nephritic flares. CONCLUSIONS The long-term prognosis of Caucasian patients with proliferative lupus nephritis may be better than usually thought. Favorable factors for good long-term outcome are the achievement of complete renal remission, the absence of nephritic flares and their complete reversibility after therapy.