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The effect of exercise training (five 45-min walking sessions/wk at 60-75% maximum heart rate) and/or moderate energy restriction (4.19-5.44 MJ or 1,200-1,300 kcal·d-1) on innate and adaptive immunity (including mitogen-stimulated lymphocyte proliferation (MSLP), natural killer cell activity (NKCA), and monocyte and granulocyte phagocytosis and oxidative burst(MGPOB) was studied in obese women (N = 91, age 45.6 ± 1.1 yr, body mass index 33.1 ± 0.6 kg·m-2) randomized to one of four groups: control (C), exercise (E), diet (D), exercise, and diet(ED).Aerobic power, body composition, and immune function were measured in all subjects before and after a 12-wk diet intervention period, with data analyzed using a 4 × 2 repeated measures design. All subjects self-reported symptoms of sickness in health logs using a precoded checklist. Statistical significance was set at P ≤ 0.05.Data from this study indicate that although exercise training was unrelated to any significant changes in resting immune function, the number of days with symptoms of upper respiratory tract infection (URTI) was reduced relative to subjects in the nonexercise groups (5.6 ± 0.9 and 9.4 ± 1.1 sickness days, respectively, P < 0.05). Energy restriction and weight loss (7.9 ± 0.7 kg) was associated with a significant decrease in MSLP, but no change in NKCA, MGPOB, or URTI.The data are consistent the viewpoint that weight loss, even at a moderate rate, is associated with a decrease in mitogen-stimulated lymphocyte proliferation without a change in various measures of innate immunity of the blood compartment.