Several immune-neuroendocrine interactions are known to occur both in primary and secondary lymphoid organs. Here, Mireille Dardenne and Wilson Savino review data obtained in humans and experimental animals showing that peptidic hormones and neuropeptides can influence the thymus pleiotropically. These mediators modulate thymic epithelial cells (TECs), affecting thymulin secretion, cytokeratin expression, production of extracellular matrix (ECM) proteins and cell growth. Interestingly, such neuroendocrine influences appear to be part of a bidirectional circuitry, since thymic-derived peptides also regulate the release of hormones from the pituitary and hypothalamus.