A previous retrospective study has found an increased risk of uterine cervical atypia in women with systemic lupus erythematosus (SLE) who have been treated with cytotoxic drugs. Our objective was to prospectively reveal any increased incidence of cervical atypia in SLE patients and to evaluate the relationship to previous chemotherapy. A total of 39 SLE women were prospectively referred for cytologic PAP smears of the uterine cervix. A significantly higher incidence of cervical atypia was found in SLE women (35.9%) compared with non-SLE control groups (< or = 5%; P < 0.01). No significant difference was found between the incidence of atypia in patients previously treated by cytotoxic medications such as cyclophosphamide pulses or methotrexate (4 of 9) compared with SLE women not receiving cytotoxic drugs (10 of 30). Colposcopically directed biopsies revealed three cases of cervical intraepithelial neoplasia (CIN) I-III (23%) among the cases with atypia. We conclude that women with SLE should have regular cytologic cervical smears because of a significantly increased incidence of atypia, regardless of previous cytotoxic therapy.