We sought to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and 89Sr-pretreated W/Wv mice. 89Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the 89Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the 89Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. We conclude that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation.