Fifteen metastatic lines derived in vivo from three syngeneic murine tumors, the sarcomas SA-NH and SA-4020 and the hepatic carcinoma HCA-I, were assessed for their stability of metastasis formation upon isotransplantation for several successive generations in syngeneic animals. Change in the metastatic phenotype was actively encouraged by a new procedure, the artificial selection for increased or decreased metastasis formation. Metastatic instability was dependent on tumor type, with five of six lines of tumor SA-NH, one of four lines of tumor SA-4020, and possibly one of five lines of HCA-I changing in lung metastasis formation. The instability of lung metastasis formation was also assessed by analyzing changes in the variance of the lines. Concomitant with a change in metastatic potential for lung metastasis, we observed a similar change for abdominal lymph node metastasis. We also report the selection of a less metastatic line. The variance of lung metastasis increased significantly only in the SA-NH lines. The instability of metastasis formation was attributed to genetic instability of metastatic cell lines.