Interactions between the immune, nervous and endocrine systems are important in inflammation and tissue repair. One neuroendocrine pathway involves polypeptide factors derived from the submandibular glands, whose synthesis and release are controlled by cervical sympathetic nerves. This novel pathway of immune-neuroendocrine communication is the cervical sympathetic trunk-submandibular gland (CST-SMG) axis. Here, Ronald Mathison, Joseph Davison and Dean Befus discuss the contributions of this axis to the neuroendocrine regulation of inflammation and tissue repair.