Voltage clamp experiments were done on single nodes of Ranvier of Rana esculenta. Equilibrium effects were obtained from INa-V curves, the rates of action from changes in INa on changing solutions during repetitive depolarizing pulses. 2. Saxitoxin (STX) exclusively and reversibly blocked Na channels, the effect being fully described by a one-to-one reaction between STX and a receptor at the channel with an equilibrium dissociation constant, Ks, of 1.4 nM; the mean offset rate constant k2s, was 1.76 X 10(-2) sec-1 (16 +/- 1 degree C;pH 7.2), 1.7 times the value for tetrodotoxin (TTX). 3. At pH 5.6, K2S WAs increased by a factor of 1.33 while the equilibrium STX effects was decreased in a way suggesting competition between STX and protons. 4. After pretreatment of nodes with 3.1 nM TTX the extra block on adding 9.0 nM STX as well as its relief on taking out STX of the TTX-STX mixture revealed transients in the time course of receptor occupation. 5. These non-monotonic time courses are incompatible with the idea of two independent blocking sites (for STX and TTX) per channel but could be quantitatively fitted by analog-computed curves assuming competition between STX and TTX for the same site.