Metastatic lines and clones of the rat 13762NF mammary adenocarcinoma have been established that show reproducible spontaneous metastasis from the mammary fat pad to regional lymph node and lung. Poorly (MTC) and highly (MTLn3) metastatic cloned lines derived from tumor growing in the mammary fat pad (MTC) and its spontaneous lung metastasis (MTLn3) were tested in vitro for their abilities to attach to and invade into syngeneic organ tissue and to survive and grow in medium conditioned by target and nontarget syngeneic organ tissues. The highly metastatic MTLn3 cells adhered to and invaded target lung tissue at significantly higher rates than the MTC cells, and bound to and invaded other organ tissues although at lower rates than lung tissue. Similarly, the MTLn3 cells showed significantly higher growth stimulation by lung-conditioned medium than medium conditioned by other tissues. Poorly metastatic MTC cells were not significantly stimulated by any of the organ-conditioned media. The results are consistent with previous proposals that explain preferential organ metastasis in terms of 'seed and soil', and further suggest that metastasis of mammary tumors to specific organ secondary sites is mediated by specific properties, such as those involved in tumor-cell organ-cell adhesion, invasion, and growth.