Endothelium and the vascular basement membrane form important barriers between the circulation and extravascular compartment. Cancer cell motility contributes to the passage of metastatic cells across this barrier, an essential step in tumor dissemination. In this study we found that the conditioned media of human endothelial monolayers contained a chemoattractant for neoplastic cells and that the chemoattractant activity was greater in the media of cultures which had been stimulated 4 h previously with 10 micrograms/ml bacterial lipopolysaccharide or the peptide formyl-L-methionyl-L-leucyl-L-phenylalanine at a concentration of 10(-6) M. The generation of this activity correlated with the expression of intracellular mRNA for interleukin 1 (IL-1) and with the presence of IL-1 biological activity in the conditioned media. The chemotactic activity in these media was lost after they had been incubated with anti-IL-1. Finally, recombinant human IL-1 alpha and IL-1 beta stimulated dose-dependent, random, and directed migration of human tumor cell populations in the Boyden chamber assay. Thus, this paper describes a mechanism by which the production of IL-1 by endothelial cells could modulate the behavior of tumor cells within the circulation.