Eleven patients with systemic lupus erythematosus (SLE) were monitored prospectively during pregnancy. Clinical and serologic features of disease activity were recorded, and after delivery, a careful search for pathologic changes in the placenta was carried out. Seven patients delivered live infants, and 4 patients had unsuccessful pregnancies, with fetal loss occurring between 12 and 27 weeks of gestation. One of these 4 patients had active SLE at delivery, and all had circulating lupus anticoagulant and thrombocytopenia. Other serologic abnormalities, including anticardiolipin and anti-Ro antibodies, were not associated with fetal loss. The overall placental size was reduced in SLE patients compared with that in healthy controls and in diabetic controls. A variety of pathologic changes were noted, including placental infarction, intraplacental hematoma, deposition of immunoglobulin and complement, and thickening of the trophoblast basement membrane. The reduction in placental size appeared to enhance the clinical significance of these pathologic changes.