The interactions which regulate haemopoiesis have been studied extensively in recent. years and a variety of humoral factors have been shown to influence the growth and differentiation of haemopoietic cells. In general, however, these humoral regulators of haemopoiesis act upon haemopoietic stem cells (HSC) which are already committed to a particular line of differentiation. The interactions which determine the function of uncommitted, pluripotential HSC have yet to be elucidated. Such evidence as is available would suggest that pluripotential HSC function is determined by close-range interaction with local or microenvironmental factors within the haemopoietic organs (Lajtha, 19 79). The haemopoietic microenvironment is a difficult entity to define. Morphologists apply the term to those elements within the haemopoietic tissue which provide mechanical support for the developing haemopoietic cells, as well as to other non-haemopoietic elements, including the vascular and neural tissues of the marrow (Weiss, 1975; Lichtman, 1981). As a functional concept, the term could broadly be applied to the totality of factors which influence haemopoietic activity. In discussing the function of the haemopoietic microenvironment, however, the term is more usually applied to factors which act at close range rather than at a distance and which are essentially permiscive rather than regulatory. A more precise definition will only become available when these factors are better understood. Perhaps the most compelling evidence supporting the existence of a permissive haemopoietic microenvironment derives from the localization of haemopoiesis to specific sites within the body. It is well established, in normal animals, that pluripotential HSC circulate freely in the peripheral blood (Everett & Perkins, 19 76). It is only in the haemopoietic tissues, however, that HSC proliferate and differentiate. In lethally-irradiated animals, after reconstitution with donor marrow cells, haemopoietic colonies develop within the bone marrow and spleen, but not elsewhere (Till & McCulloch, 1961). These observations suggest that certain organs provide microenvironments which are unique in their capacity to support haemopoiesis.

There exists a congenital hypoplastic anaemia of mice, the Steel anaemia (S1/Sld), which appears to be the result of a specific, genetically-determined defect of the haemopoietic microenvironment. Affected animals have normal HSC, which can protect recipient animals from the lethal effects of radiation. Steel anaemic mice are not cured by transfusion of stem cells from normal animals. They are, however, cured by heterotopic transplantation of