The ATP-mediated histamine release from rat peritoneal mast cells was studied in vitro by histamine assay in combination with morphological examination of the cells utilizing light and electron microscopy. It was found that ATP in the presence of calcium has strong histamine-releasing properties and that this release was accompanied by certain characteristic morphological features in the cells. Granule structure was altered, vacuoles were formed and the vacuoles communicated with the surrounding medium via peripheral pores. Expulsion of granules from the cellular domains was only rarely observed. Calcium may be of importance for the membrane fusion processes which lead to the extensive intracytoplasmic vacuolization as well as for the formation of the peripheral pores.