Brain-derived neurotrophic factor (BDNF) is involved in brain plasticity and neuronal survival. Generally, BDNF enhances synaptic activity and neurite growth, although the effect of BDNF on neuronal survival and brain plasticity following injury is equivocal. Housing rats in an enriched environment after experimental stroke enhances recovery of sensory-motor function, which is associated with a decrease in the BDNF mRNA and protein levels. We used BDNF+/− mice and wild-type littermate mice to investigate whether the decrease in the brain levels of BDNF affected motor function or infarct volume following transient occlusion of the middle cerebral artery (tMCAO) for 40 min. We found that the BDNF+/− mice had a significantly improved motor function on the rotating pole test 2 weeks after tMCAO compared with wild-type mice. When intermittently exposed to an enriched environment following tMCAO, the wild-type mice improved motor function to the same degree as BDNF+/− mice. There was no effect of BDNF reduction on infarct volume. Neurogenesis is induced following experimental stroke, and in the striatum of BDNF+/− mice significantly increased numbers of neuroblasts compared with wild-type mice were seen, both in standard and in enriched conditions. We conclude that decreasing brain levels of BDNF enhances the recovery of function following experimental stroke. © 2006 Wiley-Liss, Inc.