The interaction between toxin gamma from the venom of the scorpion Tityus serrulatus and sodium channels in skeletal muscle membranes from the frog Caudiverbera caudiverbera was studied. Sodium current from cut sartorius muscle fibers is a complex signal in which early and late components are difficult to separate. External application of Tityus gamma toxin initially blocked the early component in a voltage-dependent manner. Longer exposure to the toxin induced a complete blockade of the two components of the inward current. Application of tetrodotoxin to fibers pretreated with Tityus toxin at submaximal concentrations allowed the observation of the two distinct components of the inward current. Binding of 125I-labelled toxin to highly purified membrane fractions from the same muscle was used to establish the presence of high affinity receptors both in the transverse-tubular and in the surface membrane.