Cholecystokinin (CCK) has well-documented anxiogenic effects in animals and normal people, and panicogenic effects in patients with panic disorder, but little is known about its neuroendocrine profile. We examined neuroendocrine responses to intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, in 10 patients with panic disorder and 10 normal control subjects. Pentagastrin potently activated the hypothalamic-pituitary-adrenal (HPA) axis, but did not release growth hormone or any of several vasoactive peptides (neurokinin A, substance P, vasoactive intestinal peptide). The HPA axis response was unrelated to increases in symptoms. Panic patients did not differ from controls in neuroendocrine responses to the CCK agonist. Differential sensitivity to novelty stress accounted for the only patient-control differences in neuroendocrine profiles. The data suggest that CCK may help modulate normal HPA axis activity, but its anxiogenic effects are unrelated to its stimulatory effects on the HPA axis. Pentagastrin provides a safe and readily available probe for further study of CCK receptor systems in humans.