It has been suggested that reserpine blocks expression of delayed hypersensitivity in mice because it depletes stores of the vasoactive amine serotonin in mast cells. To determine whether mast cell serotonin or other mast cell-derived mediators are essential for delayed hypersensitivity, responses to contact sensitizers in mast cell-deficient W/Wv or Sl/Sld mice were studied. Because blood platelets represent another potential source of serotonin in delayed hypersensitivity responses, beige mice, whose platelets contain less than 1 percent of the normal levels of serotonin, were also examined. By the criteria of tissue swelling, infiltration of iodinated leukocytes, or histology, mast cell-deficient or beige mice expressed delayed hypersensitivity reactions whose intensity generally equaled or exceeded that of reactions in littermate controls. In addition, reserpine blocked delayed hypersensitivity in W/Wv and beige mice, suggesting that effects on mast cell or platelet serotonin cannot explain this drug's action in delayed hypersensitivity.