The adhesion of leukocytes to vascular endothelial cells is a highly coordinated process that is governed by a number of factors, including the expression of specific adhesion glycoproteins, physical forces generated within the microcirculation, and inflammatory mediators released by a variety of activated cells. The digestive system, with its large resident population of immune cells and its tremendous capacity to generate inflammatory mediators, has proven to be a valuable source of information on the mechanisms involved in the regulation of leukocyte-endothelial cell adhesion. This article considers some of the evolving issues that have surfaced as a consequence of the rapidly growing body of literature on this topic. Particular emphasis is devoted to unresolved issues related to the expression and shedding of endothelial cell adhesion molecules, the contribution of capillaries to the inflammatory response, and the role of mast cells, macrophages and lymphocytes in the modulation of leukocyte-endothelial cell adhesion.