Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H-estradiol. Patients with SLE manifested increased 16-hydroxylation of estrone. Diseases men differed from diseases women to the extent that only 16 alpha-hydroxyestrone was elevated in men, whereas women had elevations of both 16 alpha-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.