In accordance with our previous results, a marked release of histamine (HA) from rat peritoneal mast cells was initiated by 150 mM KCl in the absence of extracellular Ca2+. This release could be reduced by 20-60 mM tetraethylammonium (TEA) or tetramethylammonium (TMA), the non-selective K(+)-channel blockers, Ouabain, the general inhibitor of (Na+ + K+) ATP-ase, failed to produce any changes in this release. The action of TEA discriminated between the initiation of HA release evoked by different agents, producing a blockade of the K(+)-induced but not the 48/80-stimulated HA release. In total, these data suggest the presence of TEA/TMA-sensitive K(+)-channels in the mast cell membrane and their involvement in one of the possible pathways for the initiation of HA release.