There is now overwhelming evidence that cytokines, peptide hormones and neurotransmitters, as well as their receptors, are endogenous to the brain, endocrine and immune systems. Here, Edwin Blalock discusses how these shared ligands and receptors are used as a common chemical language for communication within and between the immune and neuroendocrine systems. Such communication suggests an immunoregulatory role for the brain and a sensory function for the immune system. A clearer understanding of this circuitry is dramatically altering our understanding of physiology and may profoundly affect the treatment of human disease.