Maitotoxin (MTX), a water-soluble polyether obtained from the marine dinoflagellate Gambierdiscus toxicus increased intracellular calcium in a concentration-dependent manner in fibroblasts obtained from human skin. The effect of this toxin was both saturable and of high affinity, showing an apparent half activation constant of 450 fM. The toxin did not release intracellular calcium storage compartments nor did the release of these compartments with thapsigargin or ionomycin affect the toxin response. The toxin effect was reduced significantly by pre-incubating the cells with 0.1% trypsin for 30 min, strongly suggesting that the toxin receptor is a plasmalemmal protein. The effect of MTX was partially inhibited by diphenoxylate.