Human skin mast cells were degranulated in vivo by intradermal injection of antigen. Biopsy specimens of control and stimulated skin were obtained at 5 minutes, again at 10 to 15 minutes, and analyzed by electron microscopy. Degranulation, defined as dissolution of granule contents and swelling in at least 20% of secretory granules of mast cells was observed in one third of mast cells at 5 minutes and in nearly two thirds of mast cells at 10 to 15 minutes, but was absent in biopsy specimens of control subjects. Anaphylactic degranulation was characterized by extensive fusion of granules to form degranulation channels, fusion of channels with the cell membrane to form large pores, and exocytosis of amorphous or fibrillar granule matrix into the connective tissue. Extruded secretory granules of skin mast cells persist for at least 15 minutes in the connective tissues, in apparent contrast to the process of in vivo degranulation in nasal and lung mast cells.