DEET and permethrin were implicated in the development of illnesses in some veterans of the Persian Gulf War. This study was designed to investigate the effects of daily dermal application of these chemicals, alone or in combination, on the permeability of the blood-brain barrier (BBB) and blood-testes barrier (BTB) and on sensorimotor performance in male Sprague-Dawley rats. Groups of five rats were treated with a dermal daily dose of 4, 40, or 400 mg/kg DEET in ethanol or 0.013, 0.13, or 1.3 mg/kg permethrin in ethanol for 60 d. A group of 10 rats received a daily dermal dose of ethanol and served as controls. BBB permeability was assessed by injection of an iv dose of the quaternary ammonium compound [3H]hexamethonium iodide. While permethrin produced no effect on BBB permeability, DEET alone caused a decrease in BBB permeability in brainstem. A combination of DEET and permethrin significantly decreased the BBB permeability in the cortex. BTB permeability was decreased by treatment with DEET alone and in combination with permethrin. The same animals underwent a battery of functional behavior tests 30, 45, and 60 d after exposure to evaluate their sensorimotor abilities. All treatments caused a significant decline in sensorimotor performance in a dose- and time-dependent manner. These results show that daily dermal exposure to DEET, alone or in combination with permethrin, decreased BBB permeability in certain brain regions, and impaired sensorimotor performance.