Cells prepared from liver, thymus, and spleen of fetal lambs at different stages if gestation were confronted with allogeneic and xenogeneic cells in MLC. Specific elimination of the responding cells with BUdR and UV light together with a subsequent restimulation was used to study the specificity of the reaction. The response of fetal liver cells was not based on the existence of specifically recognizing cellular subpopulations; the response was concluded to be due either to stimulatory products released by the stimulating cells or to the multipotentiality of the responding cells. Specifically recognizing cells first appeared in the thymus at 58 days postconception and in the spleen at 70 days. In the response of sheep lymphocytes against allogeneic and xenogeneic (mouse, human) cells, a cross-reactivity occurred. Fetal lamb lymphocytes were also capable of recognizing intraspecies differences on the xenogeneic cells. This capacity developed simultaneously with the specific recognition of allogeneic cells. No clear difference was observed in the reactivity of fetal thymus cells and spleen cells when compared to that of adult peripheral blood lymphocytes. These findings indicate that immunologically specific recognition of foreign cells is created in the sheep during the early intrauterine development.