We investigated whether the effects of corticosterone (CORT) on brain cell proliferation are mediated via its detrimental effect on brain-derived neurotrophic factor (BDNF). Using a [H-3]thymidine tracer study, it was demonstrated that the cell proliferation rate in the neurogenic hippocampus and subventricular zone was increased in placebo-treated adrenalectomized (ADX) mice with low plasma corticosterone levels when compared with chronically CORT-treated ADX animals (25 mg or 100 mg sustained-release pellet). The cell proliferation rate of SHAM animals was in between the ADX-placebo group and ADX CORT-treated groups. BDNF protein contents in the hippocampus and subventricular zone were not different between the SHAM group and ADX-placebo group, although BDNF contents were decreased in the chronically CORT-treated ADX animals. Thus, other factors besides BDNF are involved in mediating CORT-induced changes in cell proliferation. Further, CORT manipulations did not affect caspase-3-like activity in any of the brain regions investigated, suggesting that caspase-3 is not involved in possible CORT-induced cellular losses.