Motility factors play a major role in tumor cell invasion and metastases. The biochemical properties of various motility factors; the receptor mediated mechanism of action; the role of microtubules; the potential influence of oncogenes; and the influence of motility factors on type IV collagenase secretion and invasion are discussed. We report on expression of a 70 kDa motility factor, termed invasion stimulating factor (ISF), in human prostatic PC-3 sublines. Boyden chamber chemotactic assays and measurements of type IV collagenase synthesis and secretion suggest that an ISF-receptor dependent mechanism influences tumor cell invasion and protease secretion. Taken together, the evidence that autocrine motility factors play an essential role in tumor cell invasion and metastases is compelling.