We demonstrated that short times (15 min) of immobilization stress application induced a very rapid increase in brain-derived neurotrophic factor (BDNF) mRNA expression in rat hypothalamus followed by a BDNF protein increase. The early change in total BDNF mRNA level seems to reflect increased expression of the BDNF transcript containing exon III, which was also rapidly (15 min) modified. The paraventricular and supraoptic nuclei, two hypothalamic nuclei closely related to the stress response and known to express BDNF mRNA, were analyzed by in situ hybridization following immobilization stress. In the parvocellular region of the paraventricular nucleus, BDNF mRNA levels increased very quickly as early as 15 min. In contrast, in the two other regions examined, the lateral and ventral magnocellular regions of the paraventricular nucleus, as well as in the supraoptic nucleus, signals above control were increased later, at 60 min. After stress application, plasma adrenocorticotropic hormone and corticosterone levels were strongly and significantly increased at 15 min. These studies demonstrated that immobilization stress challenge very rapidly enhanced BDNF mRNA levels as well as the protein, suggesting that BDNF may play a role in plasticity processes related to the stress response.