BACKGROUND: Lupus, one of the most common autoimmune diseases in pregnancy, may involve multiple organ systems with varying severity. The diagnosis and treatment of the disease may be complicated by the physiologic changes of pregnancy. CASE: A 22-year-old woman presented at 29 weeks' gestation with a 4-week history of dyspnea and mild hypertension. She was found to have large bilateral pleural effusions. Her antinuclear antibody level was 1:640, with a speckled pattern, and her complement levels were low. Her urine had 2+ hemoglobin and 2+ protein with hyaline casts. Over the next three days, respiratory compromise increased despite high-dose steroids. A cesarean delivery was performed for fetal compromise. The infant did well after moderate respiratory distress. The mother developed worsening respiratory distress with adult respiratory distress syndrome, and she could not be weaned from the ventilator. Bilateral chest tubes were placed to control her effusions. Urine output remained poor despite pressors and diuretics. Staphylococcal sepsis occurred on postoperative day 5 and precluded our use of other antiinflammatory agents. Over the next 14 days the mother developed seizures, hypotension and eventual respiratory collapse. Autopsy was notable for lupus nephritis and serositis. CONCLUSION: The diagnosis and management of systemic lupus in pregnancy may be extremely difficult. Serositis and nephritis may lead to maternal compromise despite early diagnosis and treatment.