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Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., lambda-cyhalothrin) as well as enriched active isomers (e.g., gamma-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of lambda- and gamma-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for gamma-cyhalothrin was lower than for lambda-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the gamma-isomer (1.29 mg/kg) compared to lambda-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of gamma-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While gamma-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations were less, with gamma-cyhalothrin being 1.3- to 1.6-fold more potent than lambda-cyhalothrin. These potency differences are consistent with the purity of the lambda-isomer (approximately 43%) compared to the enriched isomer gamma-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of behavioral effects. Published by Elsevier Inc.