鈥� Abnormalities of hormonal responses to a number of neuroendocrine challenges have been reported in depressed patients. Most studies have examined responses in a single neuroendocrine axis. We used a series of four neuroendocrine challenges (thyrotropin-releasing hormone test, gonadotropin-releasing hormone test, insulin tolerance test, and dexamethasone suppression test) to examine eight hormonal responses in 22 healthy subjects and 22 patients with bipolar disorder. Variability of hormonal responses in bipolar patients was examined by evaluating the number of abnormal hormonal responses as compared with responses from healthy volunteers. Abnormalities were observed after all four neuroendocrine tests. Nine control subjects (40.9%) and 17 bipolar patients (77.3%) had at least one abnormal response. More strikingly, 12 bipolar patients (54.5%), but no controls, had two or more abnormal responses. These findings suggest that manic-depressive patients show increased variability in hormonal response from multiple neuroendocrine axes.