1. Tritium labelled saxitoxin has been prepared and purified, and its binding both to intact rabbit vagus nerves and to a solubilized preparation of garfish olfactory nerve membranes has been examined.2. In intact and solubilized nerves there is a saturable binding component of magnitude equal to that previously obtained for labelled tetrodotoxin.3. This component of bound saxitoxin is displaced competitively by tetrodotoxin, and it is concluded that the two toxins bind to the same site.4. The saturable saxitoxin (STX) interaction with the nerve membrane is reversible and can be described by the equation STX + R right harpoon over left harpoon STX.R where R is the binding site or receptor. With the solubilized preparation of garfish nerve membranes the saxitoxin-receptor reaction rates are almost four times faster than those of tetrodotoxin. The half-life of the saxitoxin-receptor complexes is 13 sec compared with 44 sec for the tetrodotoxin-receptor complex.5. A number of agents were tested for their ability to displace the labelled saxitoxin. Calcium and thallous ions each produced significant reversible reduction in binding, with apparent equilibrium dissociation constants of about 20-30 mM. Toxin binding is also inhibited reversibly in acidic solutions by protons competing with toxin for a binding site with a pK(a) of 5.6-5.9. All three ions are known to block sodium currents in myelinated nerve at similar concentrations. Our experiments indicate that they do so at the site of toxin binding.6. Lidocaine and veratrine do not affect the binding of saxitoxin.