Natural-killer-(NK)-cell activity and blood levels of interleukin 2 (IL-2), dehydro-epiandrosterone (DHEA), DHEA sulphate (DHEA-S) and cortisol were measured in 17 patients with major depression and 10 control subjects. Depression severity was evaluated using the Zung Self-rating Depression Scale. NK-cell activity and IL-2 levels were measured using a chromium-51 release test and an enzyme-linked immunosorbent assay, respectively. Radio-immunoassays were used to measure serum cortisol, DHEA and DHEA-S. As would be expected, patients with major depression had a higher score on the Zung Self-rating Depression Scale than healthy controls. Compared with controls, NK-cell activity and levels of cortisol and DHEA were reduced in patients with major depression, whereas IL-2 levels were increased. No difference was observed in DHEA-S levels between patients and controls. A reduction in NK-cell activity and DHEA levels, and an increase in IL-2 levels appear to be associated with major depression. Whether these changes are the cause or the consequence of the depression remains to be determined.