In rat mast cells Ca2+ 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 Ca2+ entry elicited by the intracellular Ca2+-ATPase inhibitor thapsigargin. In this work we studied the regulation of the Ca2+ entry by HCO3- and its relationship with exocytosis, The Ca2+ entry was activated by thapsigargin and Ca2+ in mast cells bathed by a HCO3--buffered medium or a HCO3--free medium, Both Ca2+ entry and exocytosis were enhanced by the presence of HCO3-ions. Nondegranulated mast cells showed a low Ca2+ entry either in the presence or absence of HCO3-. Thus, mast cells with a high [Ca2+](i) increase in a HCO3--buffered medium undergo degranulation. In the same cells a second Ca2+ entry was significantly higher than the first Ca2+ entry in a HCO3--free medium, while in a HCO3--buffered medium the first and second Ca2+ entries reached similar [Ca2+](i) levels. Although the second Ca2+ entry is high in a HCO3--free medium, degranulation is still low. Our results demonstrate that HCO3- ions increase the capacitative Ca2+ entry and the sensitivity of mast cells to intracellular Ca2+ in order to induce degranulation.