Objective: To evaluate the potential role of immunologic mechanisms that involve mast cell degranulation (anaphylaxis) or complement activation in the mechanism of amniotic fluid embolism., Methods: This study was a case series of nine women with presumed amniotic fluid embolism and a control group of 22 women who had normal labor. Women were from community and tertiary referral hospitals in Japan and the United States. Main outcome measures were maternal peripartum complement levels (C3 and C4), serum levels of tryptase, urinary histamine concentrations, and serum levels of a fetal antigen (sialyl Tn)., Results: Serum tryptase and urinary histamine measurements were negative in women with amniotic fluid embolism; seven of nine had elevated levels of fetal antigen. All eight who had serum available for testing had abnormally low levels of complement. Mean C3 level of 44.0 mg/dL and C4 level of 10.7 mg/dL were significantly lower than corresponding postpartum control values of 117.3 mg/dL and 29.4 mg/dL (P =.018 for C3, P =.012 for C4). Postpartum C3 and C4 levels decreased by 8% and 5%, respectively, compared with intrapartum values (P =.003 for C3, P =.021 for C4) but were still within normal range., Conclusion: Serologic findings suggest a role for complement activation in the mechanism of amniotic fluid embolism. Laboratory data from this series did not implicate mast cell degranulation (anaphylaxis) in the pathophysiology of the disease.