Stellate cells and immune cells are both active participants in the pathogenesis of liver disease. Interactions between these two populations are important determinants of disease outcome. Kupffer cells, neutrophils, and lymphocytes all have the potential to influence stellate cells. They produce a host of humoral mediators, including oxidants, nitric oxide, cytokines, eicosanoids, and proteinases, which can affect stellate cell proliferation, gene expression, and contractility. One important feature of stellate cell-immune cell interactions is that they are bidirectional. Not only do stellate cells receive signals from leukocytes, but they also elaborate signals that target leukocytes. Specifically, stellate cells can promote leukocyte chemotaxis and adherence, and they may also influence leukocyte activation by producing regulatory cytokines. Studies in culture provide an important background for understanding the effects of specific mediators on stellate cells and immune cells. Experiments in vivo offer an important adjunct, but often lead to confounding effects that limit interpretation. Both types of studies are required to develop a better understanding of the complex interplay between stellate cells and leukocytes.