Two low metastatic clones, NL-14 and NL-44, had been isolated from the murine colon 26 adenocarcinoma after in vivo selection and subsequent in vitro cloning. NL-14 is defective in the ability to induce platelet aggregation, but it has good in vivo growth potential. NL-44 possesses low growth potential after s.c. inoculation, but it has strong platelet-aggregating ability. A ouabain-resistant variant of NL-14 and a G418-resistant variant of NL-44 were established. Each resistant cell line conserved the phenotypes of platelet-aggregating ability or in vivo growth potential as compared to the respective parental cell line. These two clones were fused to examine the metastatic potential of hybridomas. Of eight hybridomas tested, six possessed both platelet-aggregating ability and good in vivo growth potential. These six hybridomas formed a higher number of pulmonary metastases after i.v. inoculation than the parental cells. Of the two low metastatic hybridomas, one was lacking in the ability to induce platelet aggregation, and the other showed the least potential for in vivo growth. Hybridoma clones with high platelet-aggregating activity in vitro were generally arrested well in the lung following i.v. inoculation. These results suggest that platelet-aggregating ability and in vivo growth potential are two major determinants for successful experimental lung metastasis of the colon 26 adenocarcinoma.