Perhydrohistrionicotoxin, at concentrations of 10(-12)-10(-7) M, depressed the current generated by iontophoretic application of acetylcholine to endplate regions of soleus and extensor digitorum longus muscles of rats. However, no changes in the amplitude or time course of spontaneous miniature endplate potentials or currents were seen with these concentrations of toxin. Evoked endplate currents were also unaffected by the toxin. Similarly, the responses to iontophoretic acetylcholine were depressed by these concentrations of perhydrohistrionicotoxin in chronically denervated muscles. Depression of responses in both normal and chronically denervated muscles developed gradually, was greater at higher concentrations, and was reversible. The different effects of the toxin on neurally evoked currents and currents produced by iontophoretic application of acetylcholine raise the possibility of the existence of two different population of receptor complexes.