1. This paper reviews recent findings on cellular and humoral immunity and inflammatory markers in depression. 2. It is shown that major depression may be accompanied by systemic immune activation or an inflammatory response with involvement of phagocytic (monocytes, neutrophils) cells, T cell activation, B cell proliferation, an "acute" phase response with increased plasma levels of positive and decreased levels of negative acute phase proteins, higher autoantibody (antinuclear, antiphospholipid) titers, increased prostaglandin secretion, disorders in exopeptidase enzymes, such as dipeptidyl peptidase IV, and increased production of interleukin (IL)-1 beta and IL-6 by peripheral blood mononuclear cells. 3. It is hypothesized that increased monocytic production of interleukins (Il-1 beta and Il-6) in severe depression may constitute key phenomena underlying the various aspects of the immune and "acute" phase response, while contributing to hypothalamic-pituitary-adrenal-axis hyperactivity, disorders in serotonin metabolism, and to the vegetative symptoms (i.e. the sickness behavior) of severe depression.