Experimental advances in prenatal diagnosis and fetal imaging, combined with the information from the human genome project will lead to the prenatal diagnosis of most genetic diseases in the near future. This creates an enormous therapeutic opportunity for prenatal cellular transplantation prior to the evolution of devastating congenital disease. Candidate diseases include hemoglobinopathy, immunodeficiency, errors in metabolism, and neuromuscular diseases such as muscular dystrophy. The ability to tolerize the early gestational fetus to foreign antigens because of its immunologic immaturity provides significant advantages for such treatment when compared to the neonate or adult. Additionally, this model permits a systematic analysis of the innate and adaptive immunologic mechanisms leading to self-recognition. Understanding these mechanisms is fundamental to the clinical application of allogeneic bone marrow transplantation for congenital and neoplastic diseases.