(1). The effects of benzene and several of its derivatives on sodium currents in the voltage-clamped squid giant axon have been studied. Substances tested were benzene, aniline, benzyl alcohol, propiophenone, 4-amino-propiophenone, methyl benzoate, ethyl benzoate, and 4-amino ethyl benzoate (benzocaine). (2.) All substances tested reduced the sodium current in both intact axons and axons internally perfused with CsF. (3.) There were four major actions of benzene on the sodium current: (a) an increase in the resting level of inactivation, (b) an increase in the depolarization required to produce the maximum current, (c) a decrease in the maximum sodium conductance, and (d) an increase in the rate of inactivation. (4.) 4-amino ethyl benzoate (benzocaine) had actions on the sodium current which were very similar to those of benzene with the exception that the rate of inactivation was scarcely affected and, at comparable shifts, the slope of the steady state inactivation curve was slightly smaller. (5.) The results obtained with the substances structurally intermediate between benzene and 4-amino ethyl benzoate allow some conclusions to be drawn as to the role of each functional group.