The autonomic innervation of the lymphoid tissue is currently visualized as a channel for neural regulation of immunity. Several reports have dealt with the alteration of antibody responses of spleen and lymph nodes following sympathectomy, and less often, parasympa-thectomy. This article reviwes published data on the local effects of sympathetic and parasympathetic neurons innervating immunocompetent organs on immune responsiveness. A model comprising bilateral lymphoid organs (the submaxillary lymph nodes) and the local ipsilateral manipulation of their regional sympathetic nerves (derived from the superior cervical ganglia) and of their regional parasympathetic nerves (conveyed through the lingual nerve-chorda tympani) allowed the description of purely local effects of the autonomic nerves independent of the systemic effects of the surgical manipulation itself. By employing this model, the following were observed. (1) After the unilateral sympathetic denervation of murine submaxillary lymph nodes by superior cervical ganglionectomy (SCGx), ipsilateral increases in plate-forming cell (PFC) activity, delayed hypersensitivity and graft-versus-host reactions were observed as compared to the contralateral, sham-operated, submaxillary lymph nodes. During degeneration of peripheral sympathetic nerves shortly after SCGx, PFC activity in ipsilateral submaxillary lymph nodes decreased significantly. (2) The local parasympathetic decentralization of murine submaxillary lymph nodes, achieved by the unilateral section of the chorda tympani, resulted in decreases of PFC activity, when challenged 10-20 days after denervation. (3) In the course of the immune reaction induced by the injection of complete Freund's adjuvant in rats, an augmented activity of local autonomic nerves was found in the submaxillary lymph nodes, as shown by the increase of neuronal norepinephrine uptake and tyrosine hydroxylase activity (two markers of noradrenergic activity), and of neuronal choline uptake and choline acetyltransferase activity (two markers of cholinergic activity). (4) Coincident with the augmented immune response after local sympathetic denervation of submaxillary lymph nodes, the growth of transplanted tumors in the cutaneous territory was significantly impaired in rats. (5) In the absence of an intact local sympathetic innervation, the effect of the immunosuppressive drug cyclosporine in rat submaxillary lymph nodes [as assessed by the inhibition of ornithine decarboxylase (ODQ induction after complete Freund's adjuvant injection] became significantly attenuated. (6) A similar impairment of cyclosporine activity on submaxillary lymph node ODC was found in Freund's-adjuvant-treated rats subjected to a regional unilateral parasympathetic decentralization by chorda tympani section 2 weeks later. (7) In rats injected with either Freund's adjuvant or its vehicle, the sympathetic denervation of submaxillary lymph nodes by unilateral SCGx augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. The results indicate that an appropriate sympathetic and parasympathetic local environment is needed for normal immune responsiveness and immunomodu-lation.