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Pontes-de-Carvalho, Lain Carlos. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. N1H grant AI32966, by the John D. and Catherine T.MacArthur Foundation, by the United Nations Development Program/World Health Organization Special Program for Research and Training in Tropical Diseases, and by the Rockefeller Foundation. F.V. is a research assistant of the Belgian National Fund for Scientific Research and L.P.C. is a senior investigator of the Oswaldo Cruz Foundation and is a recipient of a grant from the RHAE program, Secretary of Science and Technology, Brazil. New York University Medical Center. Department of Pathology. New York, NY, USA. New York University Medical Center. Department of Pathology. New York, NY, USA. New York University Medical Center. Department of Pathology. New York, NY, USA. New York University Medical Center. Department of Pathology. New York, NY, USA. Trypanosoma cruzi trans-sialidase (TS) is a recently described enzyme whkh transfers a(2-3)-linked sialic acid from host-derived sialylated glycoconjugates to parasite surface molecules [Schenkman et al. (1991) Cell, 65, 1117]. We report here on the ability of TS to transfer sialic acid from donor sialyl-a(2-3)lactose to sialidase-treated sheep and human erythrocytes. Up to ~ 50% resialylation of both desialylated red cells could be attained. Resialylation of desialylated sheep erythrocytes restores their resistance to lysis by human complement. This ascribes a possible biological role for T.cruzi TS and demonstrates directly that sialic acid is solely responsible for preventing alternative pathway activation of human complement by sheep erythrocytes.