Upregulation of brain-derived neurotrophic factor (BDNF) mRNA expression by neuronal activity has been reported in cultured hippocampal cells and in different in vivo excitotoxic paradigms. The aim of the present study was to determine whether sensory stimulation of the whisker-to-barrel pathway alters BDNF mRNA expression in the cortex and, if so, to evaluate the specificity of this effect. To this end, a set of mystacial whiskers was unilaterally stimulated by mechanical deflection, and the expression of BDNF mRNA was analyzed in the barrel cortex by in situ hybridization (ISH) using a 35S-labeled antisense BDNF riboprobe and emulsion autoradiography. A clear-cut and specific upregulation of the BDNF mRNA expression was found at the level of the somatosensory cortex after the increased peripheral stimulation. In the barrel cortex of control mice, BDNF mRNA was present in a few cells in layers II/III and VI, whereas it was almost undetectable in layer IV. After 6 hr of whisker stimulation, increased levels of BDNF mRNA were found in layers II to VI of the contralateral barrel cortex. In layer IV, BDNF upregulation was confined to the barrels corresponding to the stimulated follicles. ISH combined with immunocytochemistry against the three calcium-binding proteins parvalbumin, calretinin, and calbindin-D28K revealed that BDNF mRNA-expressing cells do not belong to the GABAergic cell population of the barrel cortex. The present results support a role for BDNF in activity-dependent modifications of the adult cerebral cortex.