A radioimmunoassay for the feminizing metabolite 16 alpha-hydroxyestrone was applied to a variety of sera from healthy volunteers, patients with active or inactive systemic lupus erythemattlsus (SLE), and patients with other rheumatic diseases. A significant increase in this metabolite was detected in patients with SLE, especially those with active disease, compared with normal controls (P < 0.001). SLE patients were categorized as having either active or inactive disease by clinical and laboratory criteria. Many patients who had clinically and serologically active disease were found to have normal levels of this estrogenic metabolite, and several explanations for these differences are explored in this report. Despite a poor correlation of hormone levels with age, antibody levels, or complement levels in patients with SLE, those patients with the highest levels of hormone were among those whose disease was clinically most active.The hydroxylation of estradiol at the C-16 alpha position results in the production of the agonist metabolites, 16 alpha-hydroxyestrone and estriol. Studies of patients with systemic lupus erythematosus (SLE) have shown a significant increase of such 16 alpha hydroxylation in men as well as women (1). Earlier studies of patients with SLE revealed that urinary 16 alpha-hydroxyestrone was elevated in both sexes, -~