Electric responses of extremely small amplitudes (1-30 μV peak-to-peak) repeating with more-or-less definite periodicity could be induced by a variety of chemical stimulants applied to squid giant axons either extracellularly or intracellularly. The chemical stimulants studied include allethrin, aminopyridines, N-bromosuccinimide, dimethylaminopyridine, glutaraldehyde, osmium tetroxide, parachloromercuribenzoate, rose bengal, scorpion venoms and veratridine. With several mild stimulants, it was possible to evoke periodic miniature responses unaccompanied by a fall in the resting membrane potential. The frequency of miniature responses could be lowered by intracellular injection of TEA (tetraethylammonium). These miniature responses could readily be suppressed by external application of TTX (tetrodotoxin). The miniature responses evoked by 4-aminopyrine were characterized by a large variation in the frequency of responses. Cross-linking of the membrane proteins with a dilute solution of glutaraldehyde produced miniature responses repeating at progressively falling frequencies. Analyses of the processes of production of miniature responses with these and other stimulants have clarified several aspects of the physicochemical properties of the excitable sites of the axon membrane.