Sex hormones may play a major role in the pathogenesis and course of systemic lupus erythematosus (SLE). OBJECTIVE--To evaluate the immunoregulatory effect of gonadal steroids in SLE and their mechanisms of action, and to establish a correlation with the clinical and biological activity. DESIGN--Cross-sectional study of a cohort with SLE. SETTING--Outpatient SLE clinic. PATIENTS--27 patients with chronic SLE, 14 were fertile women, 8 postmenopausal women and 5 men. MEASUREMENT--Serum gonadotropins (FSH, LH), prolactin (PRL), progesterone (PG), testosterone (T), estradiol (E2) and total urinary estrogens (UE) were studied in SLE patients and in 35 healthy controls of similar age and sex. Blood and urine samples of several days of the study cycle were obtained for hormonal assay. RESULTS--An increased LH activity was observed in all groups of patients. There were no changes in serum T levels, but absence of steroid therapy increased their levels in fertile women. A decrease in E2 values in the fertile women was observed, but total UE was similar to those in controls. This suggests an alteration in intermediate estrogen metabolism. Men with SLE showed a higher levels in PG and UE than controls. Also, in both groups of women on steroid treatment, a decrease of PRL was observed compared to the controls. In the fertile women in luteal phase, there was a decrease in PG. In the fertile women with higher clinical activity in the midcycle phase, and those with higher biological activity in the luteal phase, a decrease in serum E2 was seen. CONCLUSIONS--Our results support the hypothesis that there is an alteration of intermediate metabolism of the estrogens and of the testosterone. As well, a lower production of PRL during steroid treatment, and a lower production of PG may be important contributing factors in immunomodulation of SLE. Mechanism for this action should be mediated through a stimulation of the gonadotropins as LH.