SummaryThe in vitro binding serum complement (C) components to Schistosoma mansoni worms was studied. By exposing frozen sections of adult male and female parasites to normal human serum, binding of both classical and alternative pathway C components was observed. By immunofluorescence (IFL) microscopy selective binding of C1q, C4 and C3 to the schistosomal tegument, internal structures, the intestinal tract and eggs was seen. The C4 and C3 binding was completely abolished in the presence of 10 mM EDTA. EGTA also completely inhibited binding of C4 and most of the C3 binding. These results suggest that C binding to S. mansoni adult worms occurs mostly by the classical activation pathway. However, the partial Ca2+independence of C3 binding and the demonstrated binding of the regulatory protein β1H suggests that worms are capable also of C3 binding by the alternative pathway. No C binding occurred to intact worms. Although some in vivo bound immunoglobulin appeared to be present occasionally at the parasite surface and in the gut, this material did not account for the demonstrated extensive C deposition upon incubation of frozen sections with normal human serum in vitro. Antibody independence of the observed classical pathway C binding was further indicated by binding of isolated Clq to the same structures capable of binding C components from serum