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In many strain combinations among inbred rats, intravenously injected 51Cr-labelled lymphocytes are destroyed in substantial numbers by unsensitized allogeneic hosts. Destruction of cells (referred to as natural cytotoxicity (NC)) occurs within a few hours of injection, and is characterised by a decreased accumulation of radioactivity in the lymph nodes and increased renal excretion of label by allogeneic hosts, as compared with the distribution of label in syngeneic recipients of the same cell suspension. An intact spleen is necessary for killing. The level of NC expressed is consistent for a given donor-host combination. Using arbitrary criteria to compare the levels of NC expressed by different donor-host combinations among inbred rats, 13 of 95 strain combinations have been shown to express high NC, 63 intermediate NC and 19 low NC. The level of NC expressed cannot be correlated with the extent to which donor and host differ in respect of known MHC genes. Segregation analysis has shown high NC to be controlled by at least 2 independently segregating genes, one of which is MHC-linked. It is possible to weaken or abrogate NC by the neonatal injection of bone-marrow cells from the donor strain, and to reverse this reduced reactivity by the injection of host strain lymphocytes. The substitution of either the donor (P1) or the host (P2) by the P1 X P2)F1 hybrid reduces or eliminates NC in strain combinations normally expressing high NC. It is currently uncertain whether NC can be augmented. In the single strain combination in which maturation has been studied, NC becomes evident during the 4th week of life and attains adult levels during the 6th-7th weeks. NC is at least partially radio-sensitive. Two groups of reactivities appear to be related to NC: (i) those which have been identified in the context of aberrant lymphocyte homing, and for which allogeneic lymphocytes are the targets; (ii) the group of natural resistance systems which includes NK cells, and whose reactivity is directed against a variety of other target cells.

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Summanr. The orinin <»f tlur inbred albino rat strain AS2 is destriltetl. With the exception of wenk male ~* female incompatiliility. the strain appears to be isohLstogenic and liinnozygous at all loci determininji liistocompatibilily antigens. Tlu^ weak antigen diMtinguisliing males fnnii otherwise isohistogenic feuialcs is identical in ihe \Si ami IIS strains. The AS2 strain possesses lit least one hi.stocompatibility antigen in annmon with each ii( strains .VS. BS and IIS. The AS. BS and HS strains possws identical allelcs at .i uiajor histoconipatibility lcK-as at whieh they diller from Ihe AS2 strain. Donor-lurst disparity at this linns regularly leatls to the de\el(>pment of l(>>al itraft versus hast reactions followiug the injet-tion of 50 x 10« nonnal parental strain spleen eeUs beneath (lie renal capsule of Fl hybrids. Where donor and ho.st are compatible at this locus, despite disparity al up to 3 other loti detrnniiiini,' strong antigens. lotal jtriift versus host r^-actions do not occur follnwiny nonnal spleen tell transfer. altlioii(ih they occur souiewlinl irregularly if speeilically sensiUseil spleen donors are used. It therc'forc seems likely that this major locus is the .Ay-B locus. Mraii skin Kraft survival tirin-s are onl>' slightly shorter in .Xit-B incompatible combinations than in tliose combinations which are compatible at AK-B but differ in re.sjnxt of other strong histoumipatibility antigens. Parental strain -* F2 hybrid skin grafts show tlie closely related .\S and AS2 strains tu differ from each other at an estimated 4-5 liiitucunipatibilitj' loti. one of which is the Ag-B Im-ns.INTRODUCTION.