Pyrethroid insecticides are toxic to insects and mammals through effects on ion channels in the nervous system, with probable additional sites in muscle. Voltage-gated sodium channels (VGSCs) have been studied most extensively as target sites and there is evidence for two toxicity syndromes (types I and II), associated with different effects on VGSCs, based on the absence or presence of a cyano group in the alcohol moiety. Pyrethroids also have agonist effects on voltage-gated calcium channel subtype(s), which tend to show type I/II differences. There is also evidence for antagonist effects of type II pyrethroids on voltage and GABA-gated chloride channels. Correlations have been made between some ion channel effects and motor activity reductions and effects on the acoustic startle response in the rat. The former is non-specific for type I and II structures but the latter provides some evidence of separation of type I and II. Metabolic transformation of pyrethroids in mammals explains some of the relatively low toxicity of these insecticides in mammals versus insects. Pyrethroids are neurotoxic as the parent; oxidative and hydrolytic metabolites are considered to have little or no toxicity. A wide range of metabolic stability for commercial pyrethroids has been shown. The clinical signs of neurotoxicity following oral gavage dosing in rodents generally correlate with peak blood/plasma concentrations. Similarly, reversibility of neurotoxicity after oral gavage dosing usually occurs within 24h and correlates with large decreases in blood/plasma concentrations.