Variations in neurophysiological activity of a number of DDT-type compounds against the excised central nerve cord of the American cockroach were quantitatively analyzed using steric, hydrophobic and electronic parameters of both aromatic and benzylic substituents. The steric effect of aromatic substituents in terms of van der Waals volume was found to play the most significant role in determining variations in activity of DDT, DDD and prolan analogs having various aromatic p, p′-substituents. For methoxychlor analogs having various benzylic substituents, van der Waals volume, the STERIMOL length parameter, L, and the hydrophobicity of substituents were found to determine variations in activity. The insecticidal activity of these classes of compounds measured by injection into the abdomen of the American cockroach, from which the oxidative metabolic factor was eliminated as far as possible by injection of piperonyl butoxide, correlated very well with neuroexcitatory activity when the transport factor was separated using the hydrophobicity parameter.