Laboratory strains of the German cockroach, Blattella germanica (L.), that were either susceptible (S, Orlando Normal) or resistant (R, Village Green) to pyrethroid insecticides were compared in studies of the topical toxicity of permethrin, as well as the in vivo penetration, metabolism, and excretion of radioactive material after topical application of sublethal doses of [C-14]trans-permethrin. The objective of these tests, which were done in the presence or absence of the metabolic synergists PBO or DEF, was to obtain a better idea of the possible contribution to resistance of factors other than a previously identified kdr-like mechanism. Toxicity tests indicated the R cockroaches were highly resistant to permethrin (R/S value 38.9). Pretreatment of insects with PBO or DEF strongly increased the toxicity of permethrin to both S and R strains but did not change the level of resistance; the R/S value with PBO was 42.8 and with DEF was 41.5. Cuticular penetration, internal accumulation, and excretion of radioactive material were all slower in R strain insects. Coadministration of [C-14]trans-permethrin with the synergists reduced its cuticular penetration and the subsequent excretion of radioactive material in both strains; internal accumulation of radioactive material was increased in both strains by PBO but was not affected by DEF. The in vivo degradation of [C-14]trans-permethrin was diminished in both strains by the two synergists, with PBO having the greatest effect. The results suggest that resistance to permethrin in this R strain is influenced primarily by the development of a kdr-like form of insensitivity in neural target sites. This factor might be complemented to some extent by reduced cuticular penetration. Metabolic degradation is a very important defensive mechanism in both S and R strains but does not appear to be enhanced in the R strain to the extent that it could be considered a major contributing factor in resistance.