Acute stress evokes immediate responses in the cardiovascular endocrine, and immune systems. In particular, the number and activity of natural killer (NK) lymphocytes increase after stress. Here, we investigate the possibility to pharmacologically interfere with these stress-induced immunologic changes. Twenty-five healthy males were subjected to an acute stressor, a first-time tandem parachute jump. Subjects were randomly assigned to a beta-adrenoceptor antagonist (propranolol), a benzodiazepine (alprazolam), or placebo group. To analyze the role of the spleen in lymphocyte redistribution, splenectomized subjects performed a parachute jump. Propranolol, but no alprazolam, inhibited the heart rate increase during jumping. Increases in epinephrine and cortisol in the propranolol group were comparable to placebo, but were attenuated by alprazolam. The number and activity of NK cells significantly increased in the placebo group but not in the propranolol group immediately after stress. Alprazolam treatment did not alter the increase in NK cell numbers but did inhibit the increase in NK activity. In splenectomized subjects, NK cell numbers, but not NK activity, increased as in placebo subjects. We conclude that stress-induced changes in the immune system are controlled by beta-adrenergic mechanisms and only partly depend on the spleen; central interference with alprazolam differentially affects stress-induced changes in the NK cell compartment.