A number of cytokines have been reported to increase the cell motility (scatter) of cohesive cell colonies. We report here a novel scattering factor produced by human monocytes. Media from both stimulated and non-stimulated human monocytes or the monocytic cell line, U937, increased the cell motility of 2 human colon-cancer cell lines, HT115 and HT29, but not the canine epithelial cell line MDCK. Motility was assayed by cell dissociation from carrier beads and colony scattering. HT115 cells were strongly scattered by the conditioned media but not by interleukins IL-1, 2, 4, 6, 8, 10, TNF alpha, TGF beta, EGF, GM-CSF, IGF-I, PDGF, interferon-gamma. This factor is distinct from hepatocyte growth factor/scatter factor (HGF/SF), since the activity was not blocked by anti-HGF/SF antibody. The activity was reduced by treatment with acid, heat, trypsin and dithiothreitol; this, together with gel filtration, suggests that the factor is a protein (MW 40 to 60 kDa). This new factor, which is secreted from monocytes and the monocytic cell line, U937, has the ability to increase the motility of cancer cells and may be important in controlling the behaviour of tumours in vivo.