This study evaluated the sympathoadrenal modulation of behaviorally evoked immune responses by administration of a nonselective adrenoceptor antagonist (labetalol) to subjects exposed to mental stress.In a 2 X 2 factorial design, subjects were assigned to a labetalol or saline condition and, within each condition, were exposed either to acute laboratory stress or no stress (control). Lymphocyte subsets, natural killer (NK) cell cytotoxicity, and T cell proliferation to phytohemagglutinin and concanavalin A were assessed pre-experimentally, at baseline after infusion and after 18 minutes of mental stress (or rest). By comparison with the other three conditions, the saline-stress group showed a greater peripheral NK cell number and cytotoxicity, lower mitogenic response to phytohemagglutinin and concanavalin A, and diminished ratio of CD4:CD8 cells after the stressor. As predicted, immune responses did not differ among the remaining groups (labetalol-stress, saline-rest, labetalol-rest). Group differences in NK cell cytotoxicity were not significant after controlling for differences in NK cell numbers. These findings demonstrate that the occurrence of certain immunologic responses to acute psychological stress are dependent on concomitant activation of the sympathetic nervous system.