The alcohol moiety of conventional pyrethroids is a major site of oxidative metabolism in resistant tobacco budworms, Heliothis virescens (F.). In this study, the phenoxybenzyl moiety found in conventional pyrethroids was replaced with known P450 monooxygenase inhibiting or oxidatively blocked groups. Isomers (1R/1S, cis/trans) were tested as insecticides or synergists against insecticide-susceptible tobacco budworms, or insects that expressed metabolic resistance to cypermethrin. A number of compounds with pentafluorophenyl (PFP), methylenedioxyphenyl (MDP), and propargyloxyphenyl (PP) groups had insecticidal activity that was dependent on both geometric and stereochemical configuration of the permethric acid moiety. Both trans and cis isomers of 1R-fenfluthrin, which contains a pentafluorophenyl group, suppressed insecticide resistance in Pyr-R insects suggesting that oxidative metabolism of the phenoxybenzyl alcohol is the major mechanism of resistance in this strain. In contrast, the 1S, trans- isomer of fenfluthrin was inactive. Of the methylenedioxyphenyl compounds, 1R,trans and cis isomers were toxic and partially suppressed resistance in Pyr-R larvae. Again, the 1S,trans isomer of this compound was not active either as a toxin or synergist of cypermethrin toxicity. Similarly, aS,1R, trans and cis isomers of propargyloxyphenyl compounds were insecticidal but aR,1R,analogs were inactive. Finally, of the nontoxic isomers, aR,1R,cis isomers of methylenedioxyphenyl- and propargyloxyphenyl- containing compounds significantly enhanced toxicity of cypermethrin.