Marmosets are unique in that all members may be considered to be natural blood chimeras because of the high frequency of fraternal twinning and placental vascular anastomoses between the fetuses. The mixed lymphocyte culture (MLC) reaction utilizing blood lymphocytes was evaluated to determine whether this in vitro test could detect histocompatibility differences among related and unrelated marmosets. It was found that the responses could be correlated with the probable immunogenetic relationships of these animals. Thus, an allogeneic MLC reaction in which the responding (R) and stimulating (S) cells were obtained from unrelated animals within one subspecies of marmosets (Saquinus fuscicollis illigeri) yielded a lower response than a semi-xenogeneic reaction involving R and S cells from two different subspecies of marmosets (S.f. illigeri (R) versus S.f. lagonotus (S). In contrast, MLC reactions between cells from chimeric marmoset co-twins were essentially negative, indicating specific immune tolerance. Under certain experimental conditions, however, it was suggested that the dual lymphocyte cell population from a chimeric marmoset could undergo "autostimulation" as measured by label incorporation studies. The necessity of further experiments was recognized before the data could be truly accepted as reflecting an in vitro manifestation of incompatibility between the two different genetic populations of blood lymphocytes from a chimera.