BURNET and FENNER (The Production of Antibodies, Melbourne, 1949) have suggested that animals would not show an immunological response to antigens which they had previously encountered in fetal life. Dizy-gotic twins of cattle (OWEN et al., J. Hered., 1946, v, 37, 291) and man (DUNSFORD et al., Brit. Med. J., 1953, July 11, 81) have been found to behave in this way towards their red cell antigens. The present paper describes how animals may acquire tolerance to skin grafts derived from genetically unrelated stocks following prenatal exposure to the donor's tissues.

Skin grafts from A-line mice survive 11±0.3 days on normal CBA mice. CBA mice which have already destroyed one A-line graft, destroy a second graft more rapidly (< 6 days) and may be said to be immunized. Immunity to A-line grafts can be passively transferred to a normal CBA mouse by the intraperitoneal transplantation of the chopped lymph nodes of an immunized CBA mouse [see MITCHISON, below, p. 892]. If the foetuses of a pregnant CBA mouse are injected in utero with a mince of various tissues from normal adult A-line mice, then, after reaching adult life, many of the injected animals will tolerate the presence of an A-line graft indefinitely. The tissue mince does not have to include epithelium to be effective. The tolerance acquired by these mice is not due to an alteration in the antigenic structure of the grafts, since these are rapidly destroyed when the hosts are passively immunized by lymph node transplantation. It is therefore concluded that tolerance is due to the absence of an immunological response by the host. This phenomenon is strictly specific, since CBA mice tolerant of A-line skin still destroy AU-line grafts. The tolerance of newborn mice is neither raised nor lowered by the injection of foreign cells.