The toxicokinetics of permethrin after single 460 mg/kg oral and 46 mg/kg intravenous doses were studied in male Sprague-Dawley rats. Serial blood samples after oral and intravenous dosage, and brain, medulla oblongata, sciatic nerve, and liver samples after oral administration were collected. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, sciatic nerve, and liver concentrations of permethrin and its metabolites, m-phenoxybenzyl alcohol and m-phenoxybenzoic acid, were determined by a high-performance liquid chromatographic assay. The permethrin plasma profile could be adequately described by a two-compartment open model. For permethrin, the elimination half-life (t1/2 beta) and the mean residence time from plasma were 8.67 and 11.19 hr after i.v. and 12.37 and 17.77 hr after po administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.058 liter/hr. After the single oral dose, permethrin was absorbed slowly with a Tmax of 3.52 hr. The maximum plasma concentration was 49.46 micrograms/ml. The oral bioavailability of permethrin was found to be 60.69%. The plasma concentration-time data for permethrin metabolites as well as the tissue concentration-time data for permethrin and its metabolites after an oral dose of permethrin were found to fit a one-compartment open model. The elimination half-life (t1/2el) of permethrin was greater for the hippocampus, medulla oblongata, frontal cortex, and sciatic nerve (23.10, 22.36, 13.86, and 16.27 hr, respectively) than for plasma (t1/2 beta, 12.37 hr). The maximum amounts of permethrin in cerebellum, hippocampus, caudate putamen, frontal cortex, hypothalamus, and sciatic nerve were about 1.5, 2, 2, 2.7, 4.8, and 7.5 times higher than in plasma, respectively, indicating an accumulation of pyrethroid by nervous tissue itself. Nervous tissue accumulation of permethrin was also reflected by the area under the concentration curve ratios of tissue/plasma (1.16, 3.71, 1.57, 4.27, 3.48, and 8.77, respectively). The metabolites of permethrin, m-phenoxy-benzyl alcohol and m-phenoxybenzoic acid, were detected in plasma and in all selected tissues for 48 hr after dosing, suggesting that a combination of metabolism by the tissues and diffusion into it from the blood may be present.