In progressive IgA-nephropathy (IgAN) no established therapy exists. We have analyzed the clinical course of 40 patients with progressive IgAN with tonsillectomy combined with cyclophosphamide (TE/CTX), high dose immunoglobulins (IVIG), or cyclophosphamide pulses (CyP), and 8 untreated patients as historical controls. Serum creatinine >250 micromol/l at beginning, proteinuria >2.5 g/l, and age >51 years were significant predictors for end stage renal failure in Cox regression analysis. In linear regression analysis, the decline of renal function significantly decreased only in patients after CyP from 29.7% per year to 2.8% per year. Proteinuria significantly decreased only in patients after CyP from 1.3 g/l to 1.1 g/l. IVIG had no maintained long term effect on renal function, and TE/CTX had no significant influence on renal function. In Kaplan Meier analysis, patients with CyP had a significantly higher cumulative probability of renal survival compared to the other patients. In conclusion, TE/CTX is not recommended in patients with advanced, progressive IgAN, if not surgically indicated. IVIG had no long-term effect on progression of IgAN. CyP therapy is able to stop the loss of renal function and decreases proteinuria in patients with progressive IgAN.