Evidence from many fields, including immunology, neuroscience, endocrinology, and behavioral medicine, points toward bidirectional communication channels between the nervous system and immune system. The nervous system may influence the immune system through two major outflow channels:(1) neuroendocrine release of neurohormones that then can travel via the circulation to immune effector organs, and (2) direct autonomic innervation of lymphoid organs. The presence of autonomic nerve fibers in lymphoid tissue provides a possible anatomical link between the nervous and immune systems that can translate central nervous system (CNS) activity into signals that in turn can influence cells of the immune system. In light of findings from our laboratories and others that (1) noradrenergic (NA) nerve fibers are present in specific lymphoid compartments,(2) norepinephrine (NE) is released from nerve fiber following stimulation,(3) cells of the immune system possess adrenoceptors. and (4) surgical and pharmacological manipulation of NA fibers result in predictable altered immune responses (see D. Felten et al., 1987b, for review), we have proposed that NE in the spleen fulfills the criteria for neurotransmission. Recent work from our laboratory has focused on aspects of development, aging, and plasticity of NA innervation of lymphoid organs to seek new insights into its role in modulation of the immune system.