Cytokines are a group of secreted proteins that exhibit diverse biological activity and are especially important in immune and inflammatory responses. The inappropriate production of cytokines in the central nervous system (CNS) has been implicated in a number of disease states such as Alzheimer′s disease, multiple sclerosis, and AIDS dementia complex. This article focuses on the biological role of three cytokines in the CNS, interleukin-6 (IL-6), tumor necrosis factor alpha, and nerve growth factor, with an emphasis on production by glial cells. We will discuss the diverse intracellular signaling pathways that regulate expression of these cytokines by glial cells and then describe the second messenger systems that mediate cytokine-induced responses in the CNS, with an emphasis on adhesion molecule expression. We conclude by discussing the complexities of signal transduction pathways, particularly “cross-talk” between different intracellular mediators. © 1995 Academic Press, Inc.