We have previously reported our experience with the use of alternate-day prednisone in the treatment of 6 patients with IgA nephropathy who have clinical or pathological risk factors for disease progression. We have now treated a total of 13 patients and followed them from 4 to 10 years. Patients received an alternate-morning dose of prednisone for 2-4 years. Dosage began at 60 mg/m2 for 3 month, was reduced to 30 mg/m2 by 1 year and 15 mg/m2 by 2 years. At last observation, urinary protein excretion was normal in 12 patients and no patient had hematuria. Twelve patients had normal estimated glomerular filtration rate (GFR) and one had renal insufficiency (GFR = 38 ml/min per 1.73 m2). A renal biopsy was performed in 11 patients after 2 years of treatment. Activity score decreased from 5.2 to 4.3 (P = 0.03) and chronicity score increased from 2.2 to 2.8 (P = 0.12). There were no complications of treatment. When compared with a historical group, the treated patients had a significant improvement in urinalysis (P < 0.00001) and preservation of normal GFR (P = 0.03). We conclude that alternate-day prednisone therapy may benefit patients with IgA nephropathy. A large prospective controlled trial is needed.