A B S T R A C T The effects of detergents on squid giant axon action and resting potentials as well as membrane conductances in the voltage clamp have been studied. Anionic detergents (sodium lauryl sulfate, 0.1 to 1.0 rn~; dimethyl benzene sulfonate, 1 to 20 mu, pH 7.6) cause a temporary increase and a later decrease of action potential height and the value of the resting potential. Cationic detergent (cetyl trimethyl ammonium chloride, 6 X 10-5~ or more, pH 7.6) generally brings about immediate and irreversible decreases in the action and resting potentials. Non-ionic detergent (tween 80, 0.1 M, pH 7.6) causes a slight reversible reduction of action potential height without affecting the value of the resting potential. Both anionic and cationic detergents generally decrease the sodium and potassium conductances irreversibly. The effect of non-ionic detergent is to decrease the sodium conductance reversibly, leaving the potassium conductance almost unchanged.