Human mast cells from adenoids show when resuspended in medium containing 10(-3) M CaCl2 after their temporary exposure to Ca2+-free saline for about 20 min an irreversible reduction of responsiveness to a variety of stimuli: The histamine release induced by concanavalin A or ionophore A 23187 is only 30-50% of the one obtained in cells which were kept in 10(-3) M Ca2+ throughout the experiment. This phenomenon called 'calcium paradox' can be almost entirely avoided if the cells are temporarily exposed to 10(-4) M Ca2+ instead of Ca2+-free saline. Number yields, average histamine contents of mast cells and the rate of the spontaneous histamine release are not affected by the transitory lack of Ca2+, nor is the histamine release enhancing effect of adenosine. At 10(-3) M Ca2+ concentration the calcium antagonists verapamil or gallopamil cause a significant inhibition of the Con A-induced histamine release only at concentrations much higher (10(-4) M than those effective in smooth muscle preparations. The actions of both calcium antagonists were not affected by the presence of added extracellular adenosine.