The interactions of metastatic variants of the B16 and K-1735 melanoma cell lines with intact capillaries isolated from rabbit brain were studied in vitro. The abilities of various cells to attach to and flatten out on the surface of blood vessels were monitored with phase contrast and scanning electron microscopy. In general, cells highly metastatic in vivo were capable of attaching to and flattening out on the surface of capillaries at a faster rate than cells of low metastatic potential or normal cells. In addition, K-1735 melanoma cells and normal fibroblasts were labeled with 125I-iododeoxyuridine, incubated with capillaries, and subsequently passed through filters. This procedure separated unattached cells from cells attached to capillaries. This assay provided quantitative information on the adhesion of metastatic tumor cells and normal cells to capillaries. Tumor cells attached to capillaries in significantly greater numbers than normal cells. Cells with high metastatic potential attached to the capillaries in greater numbers than cells with low metastatic potential, but not significantly. This model may be useful for elucidating some of the mechanisms involved in tumor cell attachment and penetration of the capillary wall during intravasation in vivo.