Evidence is rapidly accumulating to support the existence of a neuroimmune axis. However, the precise role of individual neurotransmitters in regulating immune function remains to be elucidated. In this review we focus on the role of vasoactive intestinal peptide (VIP) in modulation of lymphocyte function. We examine its status as a neurotransmitter, including evidence for neuronal and possible extraneuronal sites of synthesis. Further, we present data to demonstrate the presence of VIP receptors in human lymphocytes and, using the Molt 4b lymphoblastic cell line as a model, show VIP-mediated activation of adenylate cyclase leading to cAMP-dependent protein kinase-mediated phosphorylation of a specific Molt protein. Finally, we discuss the functional significance of VIP receptors on lymphocytes and present a model of neuropeptide-induced inflammation with possible therapeutic applications of this exciting new field of neuroimmunology.