The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.