Four new soluble placental tissue proteins (PP18, PP19, PP20, PP21) have been isolated to purity from saline extracts of human term placentas. Two of the new proteins appear to be partly associated with placental membranes; they also could be detected in placental protein fractions obtained by extracting the insoluble part of the placental tissue with solubilizing agents after the soluble material had been removed by washing with saline. The new placental proteins were characterized by their physical properties as well as by their carbohydrate and aminoacid compositions. Specific antisera to the new proteins were obtained by immunizing animals with the corresponding purified proteins. They were used to detect and quantitate the new proteins in extracts of placentas and other human tissues by immunochemical methods. From one human term placenta an average of 2 mg PP18, 90 mg PP19, 0.5 mg PP20, and around 7 mg PP21 could be extracted. None of these new proteins is specific to the placenta; they also were found to occur in extracts of certain other human tissues. The immunohistochemical localization of these proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays are presently under investigation.