The migration patterns of normal mouse embryo fibroblast (MEF) cells and mouse fibrosarcoma (FS) cells were compared in two assay systems. The two assay systems used were themodified Boyden chamber (micropore membrane) assay and the agarose drop explant assay. In both assays the major population of MEF cells exhibited a greater rate of migration than the major population of FS cells. However, a small subpopulation of FS cells which had a much greater rate of migration than the major population of either MEF or FS cells was detected in the agarose drop assay. A number of drugs which are known to inhibit the migration of leukocytes were tested against the MEF and FS cells. Concentrations were found that inhibited the major population of both groups by greater than 90%. However, at concentrations which inhibited the migration of the major population of FS cells by greater than 90%, a small group of fast-moving cells was still detected. Although the fast-moving cells were relatively resistant to treatment with the various drugs, this group was sensitive to a factor in serum. When normal human serum was used in place of fetal calf serum, the migration of the major population of FS cells was inhibited very little but movement of the fast-moving population was completely eliminated. We speculate that the small subgroup of fast-moving cells may be responsible for the invasive nature of the FS cells.