Four B16 melanoma cell variants were investigated to determine if there exists a correlation between their deformability and their metastatic potential. Cell deformability was measured as the percentage of cells traversing 10-mum diameter Nuclepore filter membranes at constant pressure as a function of time. A method was devised to circumvent common problems encountered in cell filtration experiments, i.e., cell aggregation and adhesion to the filter and failure to recover the input. F1a cells with the lowest spontaneous metastatic rate required 44 s for 50% of the cell input to traverse the filter, whereas No. 4 cells, featuring the highest metastatic rate, needed 12 s despite the fact that the cells had identical dimensions. Other variants tested showed intermediate filterability which also correlated with their metastatic potential. Cells, when pretreated with cytochalasin B at a final concentration of 21 microM exhibited increased filterability (75% and 42% greater than control for F1a and No. 4 cells, respectively). Somewhat smaller increases were observed after colchicine treatment. The findings imply major involvement of the cytoskeleton in the filterability and thus deformability of these B16 variants. Such physiochemical factors may play an important role in the metastasis of this and possibly other tumor types.