The ability of olfaction to modulate behavior in mammalian species has repeatedly been demonstrated. Here we tested the properties of the volatile components of lemon essential oil. Male and female rats were allowed to inhale the aroma while experiencing a persistent nociceptive input (50 microl formalin, 5%); in the same animals the c-Fos immunohistochemistry was used to test the degree of neuronal activation of areas belonging to the limbic system. In formalin-treated animals, lemon essential oil decreased licking the injected paw, in both sexes; flinching and flexing were decreased in males and increased in females in the interphase (5-20 min) of the formalin test. Essential oil increased the c-Fos expression in the arcuate n. of the hypothalamus. Essential oil and formalin increased c-Fos in the paraventricular n. of the hypothalamus and in the dentate gyrus of the hippocampus. In the paraventricular n. of the thalamus formalin induced higher c-Fos than control in both sexes; when formalin treatment was carried out in presence of essential oil, c-Fos further increased in males, but remained at control levels in females. The present results clearly indicate the ability of lemon essential oil to modulate the behavioral and neuronal responses related to nociception and pain.