Numerous investigations of the mammalian hematopoietic system in normal and pathologic states have been facilitated by the study of genetically determined immunologic dysfunctions in experimental animals. This article focuses on the scid mutation of the mouse (SCID mouse) that causes severe defects in the development of the immune system. The mutation appears to impair the recombination of antigen receptor genes, causing in the SCID mice a lack of functional T and B lymphocytes. Other hematopoietic cell types appear to develop and function normally. SCID mice readily support normal lymphocyte differentiation and can be reconstituted with normal lymphocytes from syngeneic or allogeneic mice and even partially reconstituted with human lymphocytes. They also support the growth of allogeneic and xenogeneic tumors. Thus, SCID mice might be useful for studies of both normal and abnormal lymphocyte development and function.