Male and female Long-Evans rat pups, exposed to an oral dose of 14 mg chlorine dioxide ClO2/Kg/d (postnatal d 10), were examined for effects on brain development and for changes in thyroid activity. Body weight reductions were observed on postnatal (pn) d 11, 21, and 35. Forebrain weight and protein content were decreased on pnd 21 and 35, as were the DNA content on d 35 and the number of dendritic spines on cerebral cortical pyramidal cells, a marker for synapse formation. Otherwise, cell proliferation in the forebrain, cerebellum, and olfactory bulbs was normal, as were migration and aggregation of neuronal cells in three areas of the cerebral cortex. Histopathology of the forebrain, cerebellum, and brainstem showed no gross lesions loss of myelin, or change in the cells staining positive for Nissl substance. Serum T3 and T4 levels, as well as hepatic mitochondrial alpha-glycerophosphate dehydrogenase activity, were unchanged by ClO2 treatment. The results indicated that ClO2 may have central neurotoxic potential. No underlying antithyroid activity was evident.