Maitotoxin (MTX) is a potent marine toxin which stimulates several Ca++-dependent processes presumably through an increase in Ca++ permeability. We have examined the effect of MTX on the release of chemical mediators from human basophils and its mechanism of action. MTX (1-20 ng/ml) induced histamine release (37-100%) from both mixed leukocyte preparations and purified basophils. Histamine release activated by MTX was slow (t1/2 cis-approximately-equal-to 15 min), temperature and Ca++ dependent (optimal at 37-degrees-C and 1-2.5 mM Ca++). Sr++ ion could substitute for Ca++ in the secretory process. Digital video microscopy analysis of purified (>70%) basophils revealed that MTX (1-20 ng/ml) induced a slow and marked increase of cytosolic Ca++ levels that was temporally coincident with histamine release. MTX (1-20 ng/ml) stimulated the release of sulfidopeptide leukotriene C4 from mixed leukocyte preparations (is-approximtely-equal-to 0.5% basophils). However, purified basophils (77 +/- 7%) showed no sulfidopeptide leukotriene C4 release even in the presence of large histamine secretion (84 +/- 14%). Two organic Ca++-channel entry blockers, verapamil and diltiazem (1-30 muM) inhibited the release of histamine induced by MTX, whereas the dihydropyridine nifedipine (0.1-10 muM) caused only minimal inhibition. These results suggest that MTX represents a novel stimulus useful to study the role of Ca++ in human basophil mediator release.