Many patients with systemic lupus erythematosus (SLE) receive long-term treatment with azathioprine and prednisolone to control disease activity. In a retrospective study we evaluated the efficacy of combined treatment with azathioprine (2 mg/kg body weight/d) and low-dose prednisolone (7-12 mg/d) and the predictors of disease flares during this therapy regimen in 61 patients with SLE. We found three predictors of flares: renal disease, persistence of dsDNA antibodies for at least 1 year after the beginning of treatment and reduction in azathioprine dosage to below 2 mg/kg/d. The occurrence of flares was significantly associated with a higher rate of disease-related death. Furthermore, the persistence of dsDNA antibodies for at least 2 years was associated with progression of renal disease. We concluded that suppression of production of dsDNA antibodies with high avidity is a suitable parameter to determine efficacy of treatment and long-term outcome during combined therapy with azathioprine and low-dose prednisolone in SLE.