Young, healthy, previously inactive men were trained aerobically 40 to 50 min·d-1, 5 d·wk-1for 15 wk. They were randomly assigned to one of three medication groups: placebo, propranolol (160 mg·d-1), or atenolol (100 mg·d-1). All subjects lost weight and decreased relative body fat as a result of training. Following training, submaximal steady-state heart rates were reduced in ail groups. Maximal oxygen uptake and maximal treadmill times were also increased in all groups. The &OV0312;O2maxof the placebo increased 18.4%. While that of the atenolol group increased 19.4%, the propranolol group went up 17.0%. Aftertraining the maximal heart rate did not change in the placebo group, while treatment with propranolol and atenolol reduced at 24.6 and 21.9%, respectively. Training caused a significant decrease in the natural killer cell activity in all three groups. The placebo group had 38.8% ± 3.8 (SD) before and 29.3 ± 3.2% lysis of target cells by natural killer cells after physical conditioning, which was significantly lower (P< 0.01). The groups treated with propranolol and atenolol were also similarly decreased. The use of propranolol or atenolol had no additional significant effect on natural killer cell activity. T-cell mitogenesis stimulated with a mitogen significantly increased with conditioning. The groups given atenolol or propranolol tended to increase somewhat more than the placebo group, although this difference was not statistically significant. There was no significant change in the percentage of total lymphocytes isolated due to training or blockade. The number of mature T-lymphocytes measured by the E-rosetting technique increased significantly consequent to physical conditioning, with propranolol and/or atenolol having no additional effect. The placebo group had 65 ± 1.3% of lymphocytes as T-lymphocytes before and 74 ± 1.4% after conditioning (P< 0.05). The increased percentage of lymphocytes which formed E-rosettes (mature T-lymphocytes) occurred as activity of the natural killer cells declined. This suggests that exercise training may influence the maturation and/or function of cells of the cellular immune system.