During the past decade, considerable evidence has accrued regarding the immunologic uniqueness of human milk and of the important role that the immune system in human milk plays in protecting not only the mature, healthy newborn, but also the premature infant who is more prone to infections and the damage caused by inflammatory processes. However, there is a great deal more to learn about the prophylactic and therapeutic uses of human milk in low birth weight infants, including (1) the status of many of the host defense factors in preterm milk, (2) how to preserve the protective agents in human milk during processing and storage, (3) the dose and duration of treatment with human preterm or mature milk that will be needed to protect against a particular disorder, (4) whether non-maternal milk is as efficacious as maternal milk for these infants, and (5) in view of the concern of potential graft versus host reactions, whether it is desirable or contraindicated to maintain the leukocytes in human milk used to feed premature infants. These questions are not easily answered, but will be worthy considerations by neonatologists, clinical immunologists, epidemiologists, and others who are concerned with providing optimal nutritional/immunologic support for the premature infant.