Sexually dimorphic patterns of cortical lateralization are documented extensively in both human and animal brains. Male rats tend to exhibit pronounced right hemisphere dominance compared with females, whereas females typically exhibit more diffuse lateralization patterns and greater left hemisphere bias compared with males. Prenatal TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin) exposure produces demasculinization of male offspring sexual behavior. In previous studies, we showed a reversal of cortical dominance in rats after prenatal TCDD exposure on gestational day 18 (GD 18). The current study aimed to determine the nature of changes observed in rats exposed to TCDD on GD 8. In addition, locomotor activity was measured in male and female offspring on postnatal day (PND) 30, 60 and 90. Pregnant females were given, via gavage, a single dose of 0, 20, 60 or 180 ng kg(-1) TCDD on GD 8. Cortical depth measurements were taken in selected brain regions in offspring 3 months old that had been exposed to the 180 ng kg(-1) dose. Areas 2, 3, 17, 18a and 39 at bregmas -1.8, -3.8 and -5.8 were analyzed by quantifying digitized, enhanced images produced by a photomicroscope fitted with a special color camera. In both male and female offspring, cortical thicknesses in control brains exceeded those of exposed brains. In several brain areas of male offspring exposed to TCDD, right hemispheric dominance reversed to left hemispheric dominance. Female offspring brains showed a contrary move towards right hemisphere dominance. Motor activity in juvenile and mature animals did not differ among dose groups. These data demonstrate that prenatal exposure to TCDD reduces cortical thickness and alters the normal pattern of cortical asymmetry, a finding consistent with the sexually dimorphic behavioral effects induced by this agent.