SUMMARYWe have used the 3‐Methylcholanthrene induced T‐10 fibrosarcoma tumour cell system (H‐2bxH‐2k)F1to elucidate the possible correlation between metastatic potential, expression of individual H‐2 antigens and susceptibility to NK cells.Transfection of the non‐metastatic and NK sensitive IC9 cells (Db+, Dk‐, Kb‐, Kk‐) with theH‐2Dkgene, altered the metastatic phenotype of the parental cells, yet had no effect on the susceptibility of these tumour cells to lysis by NK and did not elicit a specific CTL response in syngeneic hosts. Variants of the metastatic and NK resistant IE7 clone (Db+, Dk+, Kb‐, Kk‐), lackingH‐2Dk, were selected by treatment with monoclonal antiH‐2Dkantibodies and complement. These variants were sensitive to NK and poorly or non metastatic. Retransfection of ‘Dk′loss’ variants with theH‐2Dkgene, resulted in the isolation of several clones expressing a wide range of metastatic phenotypes but maintained sensitivity to NK. These results indicate that theH‐2Dregion of the MHC and or closely linked genes may be involved in the complex interrelationship between targe