OBJECTIVE: There is extensive evidence that major depression, and particularly melancholia, is characterized by hypothalamic-pituitary- adrenal (HPA) axis hyperactivity as well as systemic immune activation, which may be accompanied by increased interleukin-1 beta production. Interleukin-1 beta is known to enhance HPA axis activity during an immune response. This study investigated whether interleukin-1 beta production is related to HPA axis activity in depressed subjects. METHOD: The subjects were 28 inpatients with major or minor depression and 10 normal comparison subjects. The authors measured 1) the subjects' cortisol levels after an overnight 1-mg dexamethasone suppression test (DST) and 2) mitogen-stimulated supernatant interleukin-1 beta production by peripheral blood mononuclear cells. RESULTS: Statistically significant positive correlations between interleukin-1 beta production and post-DST cortisol values were found in the study group as a whole and in the depressed and normal subgroups separately. CONCLUSIONS: It is suggested that constituents of the immune response (such as interleukin-1 beta) in major depression may contribute to HPA axis hyperfunction in that illness.