Many neuropsychiatric diseases still elude full understanding and effective therapy. It has become increasingly obvious that some of the prevailing explanations of their pathology are overly simplistic since only a small fraction of patients appear to be Stress activates the hypothalamic-pituitary-adrenal axis through CRH, leading to production of glucocorticoids that down-regulate immune responses. However, acute stress also has proinflammatory effects. We previously showed that re- straint stress, as well as CRH and its structurally related uro- cortin (Ucn), could activate mast cells and trigger mast cell- dependent vascular permeability. Here we show for the first time that human cord blood-derived cultured mast cells (hCBMC) at 10 wk, but not at 2 wk, are immunocytochemically positive for CRH and Ucn; human leukemic mast cells are weakly positive for both peptides. The ability of these mast cells to synthesize CRH and Ucn was confirmed by showing mRNA expression with RT-PCR. hCBMC (8 –14 wk) synthesize and store 1–10 ng/106 cells (10–20