The relationship between moderate exercise training (ET) (five 45-min sessions per week, brisk walking at 60 heart rate reserve for 15 wk) and changes in immune system variables and function was investigated in a group of 36 sedentary, mildly obese women. The study was conducted using a two (exercise (EX) and nonexercise (NEX) groups) by three (baseline, 6 wk, and 15 wk testing sessions) factorial design, with data analyzed using repeated measures ANOVA. The pattern of change over time between groups for number of peripheral blood lymphocytes (total), T cells (CD5), B cells (CD20), and serum IgG, IgA, and IgM levels was significantly different. This was not the case for spontaneous blastogenesis or number of T helper/inducer cells (CD4) or T cytotoxic/suppressor cells (CD8). Within-EX-group changes were characterized by significant decreases in percentage and number of total lymphocytes, and in T cell number after 6 wk, and significant increases in each of the serum immunoglobulins after both 6 and 15 wk of training. B cell number increased significantly in NEX subjects relative to baseline values at both 6 and 15 wk, with no significant changes experienced in EX subjects. In summary, these data suggest that moderate ET is not associated with an improvement in lymphocyte function but is associated with a 20% increase in serum immunoglobulins and several small changes in circulating numbers of immune system variables, highlighted by significant decreases in circulating numbers of lymphocytes, particularly the T cell subpopulation. These changes were especially apparent after 6 wk of training, with some attenuation by 15 wk.