Directional cell locomotion is displayed by many cell types both in vivo and in vitro. In many instances, persistency and directionality are imposed by external stimuli such as chemical attractants or substrate properties. Some cell types, such as fibroblasts or leukocytes, are capable of migrating in the absence of known stimuli in a pattern known as persistent random walk, where the direction of movement is maintained for at least one cell diameter before the cell performs a sudden directional change. In many examples of persistent motility, microtubules are believed to have a key role as elements that stabilize or even determine a cell's direction of movement. If disassembled, persistency is reduced or impaired. Despite some reports to the contrary, these and other observations have led to the widely accepted view that microtubules may be the overall organizers of cell geometry, polarity and motile activity. Here we report that rapid, directional locomotion of fish epidermal keratocytes is independent of the presence of microtubules. Moreover, small cytoplasmic fragments derived from the anterior lamella of these cells are capable of locomoting in a pattern indistinguishable from that of intact cells. Since these fragments contain no nucleus, microtubules or centrioles, the persistency-determining component must be sought in some other component(s) of the cytoplasm, possibly the motile machinery of the lamella itself.