Few data are available on the response of the human immune system to acute psychological stressors under controlled laboratory conditions. Young female subjects (21–41 years) showed increases in natural killer (NK) cell activity, and in the numbers of circulating CD8 suppressor/cytotoxic T cells, and natural killer lymphocytes following a brief (12 minute) stressful mental arithmetic examination. Older female subjects (65–85 years) failed to show the stress-related increase in NK activity. The psychological stress did lead to increases in the numbers of circulating CD8 suppressor/cytotoxic T cells and NK lymphocytes in old subjects to a similar degree as that seen in the young group. No changes in the numbers of helper/inducer T cells (CD4), total T cells (CD3), or B cells (CD20) were found following the stressor for either group. Cardiovascular, catecholamine, and subjective stress responses were similar for the two age groups. These results demonstrate that brief psychological stress is associated with some rapid immune cell changes, including release of CD8 suppressor/cytotoxic T cells and NK cells into circulation, and in young subjects, increases in NK activity. The absence of an NK activity increase in the older subjects indicates that NK cell mobilization and cell lysis induced by NK cells may be differentially affected by stress. The results also suggest the possibility of an age-related deficit in the up-regulation of NK activity under some environmental demands.