Macrophage activation syndrome (MAS) is a life-threatening complication seen in association with childhood inflammatory diseases, most commonly in systemic juvenile idiopathic arthritis (sJIA) 1, 2, 3. MAS has also been described in the setting of adult-onset Still’s disease (AOSD), systemic lupus erythematosus, drug reactions, and viral infections4, 5. Decrease in C3 has been documented in patients with lupus and MAS4; however, to our knowledge, hypocomplementemia has not been previously described as associated with MAS in sJIA or AOSD. We describe 2 patients with sJIA, and a third with AOSD, who developed MAS with hypocomplementemia during the acute phase of illness. Patient 1, a 9-year-old boy, presented with high quotidian fever, evanescent rash, and arthritis. He had leukocytosis (24 χ 109/l) with elevated markers of inflammation: erythrocyte sedimentation rate (ESR) 52 mm/h and C-reactive protein (CRP) 17.3 mg/dl. Liver enzymes and renal function were normal. Ferritin was 5623 ng/ml. Serologic tests for Epstein-Barr virus, parvovirus, cytomegalovirus, Lyme disease, mycoplasma, and group A streptococcus were negative. Complement levels, obtained by the primary intensive care team, showed slightly increased C3 (166 mg/dl) and normal C4 (32 mg/dl). He was discharged with a diagnosis of new-onset sJIA and prescribed indomethacin. Several days later, he returned to clinic with worsening symptoms and petechial rash. Laboratory results are shown in Table 1. Ferritin was markedly elevated. C3 and C4 were profoundly decreased. Aspartate aminotransferase (AST) was mildly elevated and platelets declined over several days from 522 χ 109/l to 167 χ 109/l. Antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), anti-Smith, anti-RNP, anti-Ro, and anti-La autoantibodies were negative. He was diagnosed with MAS secondary to sJIA and treated with pulses of methylprednisolone (30 mg/kg/dose) and intravenous immunoglobulin (IVIG; 2 g/kg); he had improvement of symptoms and decrease of ferritin levels to 1533 ng/ml. Complement levels and ferritin measured 2 weeks after steroid pulse had normalized. He has been managed subsequently with anakinra. Since starting anakinra, he has been stable, with occasional flares of mild rash and arthritis due to periodic noncompliance.