We studied recently bereaved individuals with the corticotropin-releasing hormone (CRH) stimulation test. Subjects with a bereavement complicated by a depressive illness (n = 9) had significantly higher basal plasma cortisol levels and smaller plasma adrenocorticotropic hormone (ACTH) responses to CRH than either subjects with an uncomplicated bereavement (n = 19) or normal controls (n = 34). Subjects with depressed bereavement showed ACTH responses to CRH similar to those of depressed patients (n = 30). Bereaved subjects who had received psychotropic medications in the past (n = 13), compared with those who had not (n = 15), showed significantly smaller plasma ACTH responses to CRH. Significantly more subjects with bereavement complicated by depression, as compared to subjects whose bereavement was uncomplicated, had a past history of treatment for depression. These results suggest that predisposed individuals may respond to the stress of bereavement with a depressive illness accompanied by dysregulation of the hypothalamic-pituitary-adrenal axis.