A longitudinal study of the effect of prematurity on the development of several components of the immunologic system in human milk was performed. Milk was obtained during the second through the twelfth week after parturition. The mean concentrations of lactoferrin and lysozyme were greater in preterm than in term milk during each interval of lactation. The patterns of change in these components were similar for term and preterm milk. Secretory IgA was the predominant form of IgA in preterm milk. The mean concentrations of IgA were greater in preterm milk throughout the study period. Furthermore, total and secretory IgA levels in preterm milk rose linearly during the sixth through the twelfth week, whereas the concentrations of IgA did not change in term milk during that period. In most preterm mothers, secretory IgA antibodies to Escherichia coli somatic antigens increased as lactation proceeded. These increments in specific antibodies usually did not correlate with changes in total secretory IgA. In addition, leukocyte counts in preterm milk were usually lower at two weeks and higher at 12 weeks than in term milk. Thus the concentrations of certain components of the immunologic system in human milk are altered by premature delivery. A decrease in milk volume may account for some changes, whereas certain alterations may be the result of other consequences of premature delivery or less stimulation by the premature infant.