1. The experiments were done on single myelinated nerve fibres of Rana esculenta. The rates of toxin effect were studied either by measuring the maximum rate of rise, VA, of repetitively evoked action potentials or by measuring Na currents during periodic impulses in the voltage clamp. 2. VA measurements showed that in alkaline solutions (pH up to 8-8) the offset rate was unchanged while the onset was slowed in quantitative agreement with an assumed decrease in the active cationic form of tetrodotoxin. 3. Both VA measurements and those in the voltage clamp revealed a decrease in T'off, the offset time constant and in increase in the onset time constant, T'on, as the pH was lowered. 4. For tetrodotoxin concentrations, [TTX], up to 400 nM and pH values down to 5-3 the simple relation T'on/T'off = p'R held, where p'T is the constant factor by which the Na permeability was reduced at equilibrium with a given [TTX]. 5. The agreement between kinetic and equilibrium results was also valid when, at constant [TTX] and pH. p'T was modified by the holding potential during equilibration. 6. No unequivocal explanation of the results can be given but some of their features resemble acid catalysis.