Ciguatoxins are responsible for a human seafood poisoning named ciguatera, a disease linked to the benthic dinoflagellate Gambierdiscus toxicus and acquired by eating certain contaminated fish species. These toxins are complex, lipid-soluble, cyclic-polyethers which bind with high affinity to a specific receptor site of the neuronal, voltage-sensitive Na+ channel-protein. Pharmacological studies reveal that ciguatoxins increase Na+ permeability of various excitable cell membranes, notably at the resting membrane potential. This action is attributed to modification of Na+ channels, which then remain permanently open. As a consequence, ciguatoxins evoke membrane depolarization, cause spontaneous and/or repetitive action potentials, and influence Na+-Ca2+ exchange in nerve membranes. Moreover, ciguatoxins induce mobilization of intracellular Ca2+ in nerve cells. Finally, ciguatoxins produce swelling of nerve cells due to continuous Na+ entry through toxin-opened Na+ channels, which induces an increase in intracellular Na+ concentration and an influx of water. These latter effects of ciguatoxins are prevented by blocking voltage-dependent Na+ channels and are reversed by hyperosmolar external solutions containing, in particular, D-mannitol. In conclusion, these neurocellular actions may explain some of the human neurological alterations induced by ciguatoxins and the efficacy of D-mannitol used as a clinical treatment of ciguatera.