Cytoskeletons have been prepared from microvilli isolated from the human placental syncytiotrophoblast. They contain actin and a protein similar to fimbrin. In addition, they contain calmodulin and a protein of relative molecular mass (Mr) 105 000, both of which can be released from the cytoskeletons by treatment with Ca2+. In this respect the 105 000 Mr protein is more similar to non-muscle alpha-actinin than to the intestinal microvillar protein with an Mr of 110 000. Human placental actin displays the anomalous properties of binding to phenyl-Sepharose and wheatgerm agglutinin-Sepharose, suggesting that one or more membrane glycoproteins is associated with the actin. Transferrin, presumably receptor-bound, has been identified in preparations of extensively washed placental microvillar cytoskeletons. These findings are discussed in terms of the earliest events in endocytosis and materno-fetal transfer.