Although pediatric donation of hematopoietic stem cells (HSCs) for allogeneic transplants is common in the clinical setting, the question of when children may donate HSCs in research has received little attention. Our analysis reveals that institutional review boards (IRBs) may approve children's participation as HSC donors in transplant research when it poses no more than minimal risk to them. The risks that IRBs should consider are those that result specifically from the research, as opposed to risks donors would have faced regardless of the research. Transplant protocols that expose pediatric donors to more than minimal risk can be approved by the Secretary of U.S. Department of Health and Human Services in a special category of pediatric research.