The aim of our study was to investigate whether the level of actin polymerization plays a role in the motile and tissue infiltrating behavior of malignant lymphoma cells. For a panel of cell lines derived from the murine BW5147 T-cell lymphoma, we had previously shown a correlation between experimental metastasis formation and in vitro monolayer invasion. We have analyzed the motility and the F-actin content of six nonmetastatic, noninvasive (meta-inv-) and five metastatic, invasive (meta+inv+) variants of BW5147. Fourier analysis of cell contours was used to quantify shape changes of cells. All meta+inv+ lines rapidly protruded and retracted pseudopodia, whereas only one of the six meta-inv- lines showed this type of motility. Flow cytometry of cells stained with fluorescein-labeled phalloidin showed that the motile meta+inv+ cell lines have a higher F-actin content than their nonmotile meta-inv- counterparts. The results indicate that in lymphoma cells a high level of actin polymerization is a prerequisite for the formation of pseudopodia, which in turn are necessary for infiltration of the cells into tissues, and eventually for efficient metastasis formation. A corollary of this conclusion is that regulation of actin polymerization is a possible target for intervention aimed at moderating the spread of malignant lymphoma.