There is an increased incidence of infectious disease in periparturient dairy cows. During the periparturient period there is a decline in T-lymphocyte cell subsets, which parallels a reduction in functional capacities of blood lymphocytes and neutrophils. Mechanisms responsible for these changes in immune function during the periparturient period are poorly characterized. Ten mastectomized and eight intact multiparous Jersey cows were used to determine whether the periparturient changes in peripheral blood mononuclear cell populations are the result of the physiological demands associated with the onset of lactation or whether they are a result of the act of parturition. Blood mononuclear cells were phenotyped with monoclonal antibodies against T-cell subsets, B-cells, and monocytes. Blood samples were taken frequently from before 4 to 4 wk after parturition. In intact cows, all T-cell subset populations (i.e., CD3-, CD4-, CD8-, and gamma-delta positive cells) decreased at the time of parturition, while the percentage of monocytes increased. Mastectomy eliminated the changes in leukocyte subset populations (CD3-, CD4-, and gamma-delta positive cells, and monocytes) observed in intact cows around parturition. These results indicate that the mammary gland and metabolic stresses associated with lactation influence the composition of peripheral blood mononuclear cell populations in dairy cows during the periparturient period.