Abstract The effects of a wide range of pyrethroids and DDT analogs on the membrane potential and membrane sodium currents were studied in crayfish giant axons. Compounds differed greatly in their ability to produce depolarizing afterpotentials, repetitive firing, and membrane depolarization. The differences observed at the membrane potential level could be explained by differences in the kinetics with which the insecticides interact with the nerve membrane sodium channel. The compounds containing a cyano group at the α position retain sodium channels in a modified open state persistently, depolarize the membrane, and block the action potential without causing repetitive firing. The pyrethroids without an α-cyano group and DDT analogs retain sodium channels in a modified open state only transiently, cause large depolarizing afterpotentials, and evoke repetitive firing with minimal effect on the resting potential. The effects of the phenoxybenzyl pyrethroids were found to be intermediate between these two extremes suggesting that a continuous variation exists in kinetics with which pyrethroids and DDT analogs modify sodium channels. It was not necessary to assume a second site of action to account for the variability observed. The implications of these results to the construction of quantitative structure-activity relationships is discussed.