The effects of maximal treadmill exercise on changes in the expression and distribution of peripheral blood B-lymphocytes, T-lymphocytes, and natural killer cells (NK) were examined in 20 healthy men with a mean age of 32.0 +/- 1.3 yr. The percentage and absolute number of peripheral blood mononuclear cells that reacted with specific monoclonal antibodies which bind to B-cells (anti-Leu-12 and anti-human-immunoglobulin D-delta chain-specific), T-cells (OKT3), and NK cells (anti-Leu-11 and anti-Leu-7) were enumerated by a fluorescence-activated cell sorter in samples obtained before (Pre), immediately after (Post), and 1 h after a bout of exercise to exhaustion. In contrast to earlier studies, the results of this study indicate that maximal exertion effects a decrease in the percentage, but no change in the absolute number of peripheral blood B-cells (Pre: 0.21 +/- 0.01; Post: 0.31 +/- 0.02 cells x 10(-6).ml-1). In addition, a small, transient increase in the number of peripheral blood cells reacting with surface markers associated with T-lymphocytes (Pre: 1.15 +/- 0.09; Post: 2.05 +/- 0.19 cells x 10(-6).ml-1) and a striking, transient increase in lymphocytes having NK phenotype activity (Pre: 0.34 +/- 0.03; Post: 1.51 +/- 0.19 cells x 10(-6).ml-1) were noted. All of the pre-exercise values were re-established 1 h after exercise. Whether the mobilization of cells with surface markers associated with NK activity in response to maximal exertion serves any physiologic function during periods of physical stress remains to be determined.