The effects of the duration of lactation upon lactoferrin, lysozyme, total IgA, SIgA, SIgA antibodies to Escherichia coli somatic antigens and leukocytes in human milk were investigated. Longitidinal and cross-sectional studies were performed with milk collected from women 20 to 35 years of age during the first year of lactation. Collection and storage conditions and immunologic analyses were controlled to minimize confounding variables. The concentrations of lactoferrin, total IgA, and leukocytes and the uptake of ³H-thymidine by phytohemagglutinin-stimulated lymphocytes fell during the first several weeks of lactation; afterward, the levels of lactoferrin and IgA stabilized. Approximately 90% of total IgA in human milk during the year was SIgA. Secretory IgA antibody titers to E. coli increased in some individuals studied longitudinally suggesting that the enteromammary gland pathway of SIgA antibody production was active after several weeks of lactation. Moreover, the concentrations of lysozyme, after falling to a nadir of 20 to 30 μg/ml at 2 to 4 weeks, rose to 200 to 300μg/ml by six months and remained elevated. The immunologic system in human milk undergoes remarkable changes which may represent adaptations for the recipient infant.