In rat mast cells Ca(2+) entry is modified by the presence or absence of other ions in the external medium. HCO3(-) 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 HCO3(-) and its relationship with exocytosis. The Ca(2+) entry was activated by thapsigargin and Ca(2+) in mast cells bathed by a HCO3(-)-buffered medium or a HCO3(-)-free medium. Both Ca(2+) entry and exocytosis were enhanced by the presence of HCO3(-) ions. Nondegranulated mast cells showed a low Ca(2+) entry either in the presence or absence of HCO3(-). Thus, mast cells with a high [Ca(2+)](i) increase in a HCO3(-)-buffered medium undergo degranulation. In the same cells a second Ca(2+) entry was significantly higher than the first Ca(2+) entry in a HCO3(-)-free medium, while in a HCO3(-)-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 HCO3(-)-free medium, degranulation is still low. Our results demonstrate that HCO3(-) ions increase the capacitative Ca(2+) entry and the sensitivity of mast cells to intracellular Ca(2+) in order to induce degranulation.