Pyrethroids are widely used insecticides in the United States. These insecticides are extensively used in agriculture as well as to control insect vectors of human and animal diseases. Pyrethroids are regarded as relatively safe insecticides compared to organophosphate compounds. However, there are several studies that show that exposure to certain pyethroids, either by oral, dermal or inhalation routes during unprotected handing or spraying, may result in clinical sings of neurotoxicity. Children are likely to be exposed to pyrethoids due to ingestion of soil or dust contaminated with pyrethroid spray. The main objectives of this study were to determine: 1) species dependent changes in the plasma protein binding of deltamethrin (DLM), cis-permethrin (CIS) and trans-permethrin (TRANS) in human and rat plasma; 2) age-dependent changes in plasma protein binding of DLM, CIS and TRANS in human and rat plama; and 3) the role of albumin and lipoproteins in binding of DLM, CIS and TRANS. New solvent extraction method was developed, validated and used to characterize the plasma protein binding in human and rat plasma. DLM, CIS and TRANS were bound to both albumin and lipoproteins in the plasma. The binding of all three compounds was higher to albumin compared to lipoproteins. The binding of DLM, CIS and TRANS to human and rat plasma was quantitatively different. Plasma protein binding of all three compounds was age dependent. We observed significantly higher free fractions in birth -1 week and >1 week - 4 weeks compared to adults in humans. In rat plasma, significantly greater free fraction was observed in post natal days (PND) 10 and PND 15 as compared to PND 90. Saturation binding studies were conducted in human and rat plasma to determine the values of Bmax (maximum binding capacity) and Kd (dissociation constant) for all three compounds in all age groups. The binding parameters obtained in our study will be used for the development of a physiologically-based pharmacokinetic model for childrens risk assessment.