Acute mental and physical stress lead to a marked lymphocytosis, with circulating natural killer cell numbers showing the most prominent increase. Many studies have linked these acute stress effects on lymphocytes with an increase in catecholamine levels. However, the molecular mechanisms which mediate this redistribution of lymphocytes from lymphocyte reservoirs into the circulation remain unknown. We hypothesized that this form of lymphocytosis was in part due to shedding of cell adhesion molecules from the cell surface and a subsequent detachment of lymphocytes adhering to the vascular endothelium in lymphocyte reservoirs. In this study, healthy human volunteers (n = 12) were exercised on a treadmill until exhaustion. The circulating levels of the soluble cell adhesion molecules ICAM-1 and E-Selectin were determined by ELISA. The subjects were then randomly assigned to treatment with either propranolol or metoprolol and repeated the exercise protocol after 1 week of treatment. Prior to drug treatment, soluble ICAM-1 levels rose from 258 +/- 19 to 321 +/- 28 ng/ml following exercise and returned to approximate baseline levels of 263 +/- 22 ng/ml after 1 h of rest. This highly significant effect of exercise on circulating ICAM-1 levels (p < .005) was mitigated after treatment with the beta-adrenergic antagonists. Soluble E-Selectin levels were not significantly affected by exercise. These results suggest that dynamic exercise leads to shedding of the cell adhesion molecule ICAM-1 via adrenergic mechanisms. We believe that these findings will contribute to the understanding of how physical and mental stress modulate lymphocyte migration and adhesion.