In rat mast cells Ca 2+ entry is modified by the presence or absence of other ions in the external medium. HCO − 3 ions, which modify mast cell degranulation, seemed to modulate the Ca 2+ entry elicited by the intracellular Ca 2+ -ATPase inhibitor thapsigargin. In this work we studied the regulation of the Ca 2+ entry by HCO − 3 and its relationship with exocytosis. The Ca 2+ entry was activated by thapsigargin and Ca 2+ in mast cells bathed by a HCO − 3 -buffered medium or a HCO − 3 -free medium. Both Ca 2+ entry and exocytosis were enhanced by the presence of HCO − 3 ions. Nondegranulated mast cells showed a low Ca 2+ entry either in the presence or absence of HCO − 3 . Thus, mast cells with a high [Ca 2+ ] i increase in a HCO − 3 -buffered medium undergo degranulation. In the same cells a second Ca 2+ entry was significantly higher than the first Ca 2+ entry in a HCO − 3 -free medium, while in a HCO − 3 -buffered medium the first and second Ca 2+ entries reached similar [Ca 2+ ] i levels. Although the second Ca 2+ entry is high in a HCO − 3 -free medium, degranulation is still low. Our results demonstrate that HCO − 3 ions increase the capacitative Ca 2+ entry and the sensitivity of mast cells to intracellular Ca 2+ in order to induce degranulation.