Using a new adaptation of the 51Cr release assay, it was found that plasma membrane vesicles from the human placental microvillous surface were not only capable of eliciting both cellular and humoral immunity in mice, but were also susceptible to lysis by these immune components. The production of cytotoxic cells and circulating antibody in immunized animals was only observed in the presence of Freund's complete adjuvant. The cells exhibited reactivity only against vesicles from a limited range of placentae, while the antibodies showed reactions against vesicles from a wider range of placentae. These vesicles were also susceptible to lysis by antisera raised against placental alkaline phosphatase but were resistant to attack by antibodies raised against normal human serum and HLA (multispecific) determinants and by a cytotoxic monoclonal antibody against human beta 2-microglobulin. The cellular cytotoxicity in the spleens of immunized animals could be abrogated if the cells were pretreated with AKR anti-C3H antiserum and complement. Further, in the spleens of in immunized animals, a population of cells was detected that exhibited a 'natural' cytotoxicity against several of the membrane preparations. This cytotoxicity was heat-labile, being abrogated if the cells were preincubated at 37 degrees for 4 hr before the assay, but was resistant to attack by the anti-Thy 1 antiserum. The results indicate that the use of 51Cr-labelled placental microvillous vesicles is a useful way of searching for anti-trophoblast immunity which may now be applied to the search for immune responses in pregnancy.