The adhesive properties of highly and weakly metastatic murine sarcoma (Meth A) clones were investigated. A highly metastatic clone, MH-02, preferentially adhered to type IV collagen-coated plastic dishes and to bovine pulmonary arterial endothelial cell-coated plastic dishes as compared to a weakly metastatic clone, ML-01. Pretreatment of MH-02 and ML-01 cells with antisera against MH-02 cells resulted in almost equivalent adhesiveness to type IV collagen. Preincubation of 125I-radiolabeled tumor cells with the antisera against MH-02 significantly reduced the arrest of MH-02 cells in the lung, but ML-01 cells were not affected. The number of pulmonary metastatic nodules of MH-02 cells was reduced to the same level as that of ML-01 cells by preincubation of the tumor cells with the antisera in an experimental metastasis experiment. These results indicated that the high metastatic ability of MH-02 can be attributed to its preferential adhesiveness to type IV collagen. The type IV collagen-binding proteins of MH-02 and ML-01 were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. Among several proteins which bound to type IV collagen, expression of a protein with a molecular weight of 29 kD was significantly greater in MH-02 than in ML-01. These results suggest that the greater adhesion of highly metastatic MH-02 cells to type IV collagen is due to enhanced expression of the type IV collagen-binding 29 kD protein.