Levels of BDNF mRNA and protein were measured in the rat brain using in situ hybridization and a two-site enzyme immunoassay. Under basal conditions, the highest BDNF concentration was found in the dentate gyrus (88 ng/g), while the levels in CA3 (50 ng/g), CA1 (18 ng/g) and parietal cortex (8 ng/g) were markedly lower. Following 10 min of forebrain ischemia, BDNF protein increased transiently in the dentate gyrus (to 124% of control at 6 h after the insult) and CA3 region (to 131% of control, at 1 week after the insult). In CA1 and parietal cortex, BDNF protein decreased to 73-75% of control at 24 h. In contrast, BDNF mRNA expression in dentate granule cells and CA3 pyramidal layer was transiently elevated to 287 and 293% of control, respectively, at 2 h, whereas no change was detected in CA1 or neocortex. The regional BDNF protein levels shown here correlate at least partly with regional differences in cellular resistance to ischemic damage, which is consistent with the hypothesis of a neuroprotective role of BDNF.