Inflammatory stimuli cause plasma leakage and leukocyte adhesion in venules but not in capillaries or arterioles. The specific response of venules is governed by phenotypic specialization of the venular endothelial cells. What regulates this specialized phenotype? Several recent developments have shed new light on this question and may challenge our thinking about regulation of the venular endothelial cell phenotype. In this review, we consider some of the molecular markers of venular endothelial cells, the hemodynamic and molecular factors that may regulate the phenotype of venular endothelial cells, and abnormalities in endothelial cell phenotype in disease-related angiogenesis and microvascular remodeling. The expanding list of molecular markers may help clarify the physiologic and molecular factors that regulate the phenotype of venular endothelial cells in normal development and disease.Microcirculation (2000) 7, 67–80.