Physiologic and inflammatory leukocyte trafficking are controlled by adhesion molecules on leukocytes and endothelial cells. These adhesion molecules can be grouped into four major families: integrins, immunoglobulinlike molecules, selectins, and glycoproteins serving as selectin ligands. The recent advent of gene-targeting technology in embryonal stem cells has prompted the production of mutant mice that lack individual adhesion molecules or combinations thereof. Such gene-targeted mice permit studies into the roles of adhesion molecules in acute and chronic inflammation and of the regulation and interplay between different sets of adhesion receptors in vivo. Microcirculatory studies have been indispensable to our understanding of the importance of certain adhesion molecules for different steps of leukocyte recruitment in vivo. Targeting new genes and investigating mice with combined adhesion-molecule deficiencies will help to further clarify the molecular mechanisms of leukocyte trafficking in health and disease. This article reviews the insight gained through using adhesion molecule-deficient mice, emphasizing the role of microcirculatory studies in this research.