- 3LL tumor cells inoculated intra footpad grow locally both in syngeneic and in allogeneic recipients. Yet, spontaneous lung metastases appear only in syngeneic animals or in mice which share with the tumor strain of origin both the D-end of the H-2b haplotype and the genetic background. The lack of lung metastases in allogeneic recipients is not due to tissue restrictions for tumor growth, since intravenous injections of tumor cells resulted in local primary lung tumors. The growth rate of primary intra footpad tumors or pulmonary tumors in syngeneic mice is similar to that in congenic resistant recombinant mice. From a local intra footpad tumor in BALB/c mice, 3LL cells migrate out and reach the lungs but are arrested there, since grafts of lungs from such mice onto (BALB/c X C57BL/6)F1 resulted in tumor growth. Since spontaneous metastases developed in chimeric (C3HeB X C57BL/6)F1----C3HeB mice, it appeared that immunogenetic restrictions prevent the growth of spontaneous 3LL metastases in allogeneic recipients. Further support for the notion of allograft rejection of lung metastases derived from experiments demonstrating the generation of metastases in nu/nu ICR mice but not in nu/+ heterozygous ICR animals. It thus appeared that the local allograft of the 3LL tumor elicits a reaction which prevents the growth of its metastases. This was further supported in experiments in which intravenous inoculation of 3LL cells to allogeneic recipients from which the local tumor was removed did not produce lung tumors.