Maitotoxin (MTX) depolarized the membrane of the crayfish giant axon and decreased the amplitude and maximum rate of rise of action potentials in an irreversible manner. 2. The depolarizing action of MTX was attenuated in low Ca (1 mM; 1/10 of normal concentration) solution and was also inhibited by 2 mM Co2+, 300 microM Ni/+, 1 microM nifedipine, 10 microM verapamil or 1 microM tetrodotoxin. 3. These results suggest that the depolarization by MTX in the crayfish giant axon may be related to changes not only in Ca permeability but also in Na permeability, possibly through the modification of existing Na or Ca channels and/or a new type of channel or pore induced by MTX.