Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse. Toluene has been shown to inhibit the nicotinic acetylcholine receptors. Nicotinic receptors play an important role in brain development during brain growth spurt and early adolescence. The long-term effects of neonatal and adolescent toluene exposure on behavioral responses to nicotine in early adulthood were compared. Sprague-Dawley male and female rats were treated with toluene (500 mg/kg, ip) or corn oil daily over postnatal day (PN) 4-9 or 25-30. Nicotine-induced hypothermia, antinociception, and seizure activity were examined during PN 56-60. Toluene exposure during the brain growth spurt, but not adolescence, reduced the behavioral responses to nicotine in young adult rats. However, the levels of alpha4, alpha7, and beta2 nicotinic receptors were not altered in the frontal cortex, striatum, thalamus, hippocampus, and cerebellum by neonatal toluene exposure. These results indicate that toluene exposure during the brain growth spurt produces long-term changes in nicotine sensitivity, which may be unrelated to the total expression levels of alpha4, alpha7, and beta2 nicotinic receptors. The alterations in nicotine sensitivity may be related to the neurobehavioral disturbance associated with fetal solvent syndrome.