Cells from TS/A, a metastasizing line derived from a spontaneous BALB/c mouse mammary adenocarcinoma, were injected either sc or iv in syngeneic mice, and the resulting lung metastases or lung colonies were briefly cultured in vitro and reinjected in mice by the same route; this procedure was repeated 10 times. All the variants obtained did not show a metastatic capacity higher than the parental cell line. Moreover, they gave a number of metastases significantly lower than that produced by high metastatic clones selected in vitro from TS/A. The number of lung colonies obtained with intravenously selected (COL) variants was significantly higher than that obtained with subcutaneously selected (META) variants, TS/A, or in vitro-selected clones; this was already observable after the first cycle of selection. Both COL and META variants did not show the in vitro growth properties of the in vitro-selected high metastatic clones. In conclusion, both intravenous and subcutaneous selection procedures did not lead to an enrichment in high metastatic populations, even if such populations were present in the parental line and had been cloned in vitro; only the intravenous procedure selected high-colonizing variants.