There is no evidence on whether or not CA3 has any influence on the process of neurogenesis within the dentate gyrus, or on the ability of drugs such as fluoxetine to increase it. Should this occur, it would add a new dimension to our knowledge of the way that neurogenesis is controlled from within the hippocampus. It might also suggest additional sites of action for systemic agents, such as glucocorticoids, that control neurogenesis. In this paper, we report the effects of small, highly-localised, unilateral lesions of CA3 on the basal levels of mitosis in the progenitor cells lining the innermost region of the granule cell layer of the dentate gyrus, on the survival of newly-formed neurons, and whether these lesions alter the mitotic response of progenitor cells to the SSRI fluoxetine. We also explore the effects these lesions have on the expression of BDNF, pCREB and Wnt3a, all known to be concerned in the regulation of progenitor cell mitosis, and on markers of synapse formation and neuronal BI-D1870 maturation in the dentate gyrus. Both previous experiments had shown that basal levels of mitosis in the progenitor cells were not altered by CA3 lesions, although subsequent survival of these cells were highly compromised. There is evidence that the requirements for increasing mitosis may differ from basal conditions. For example, blocking trkB receptors has no effect on basal rates, but prevents fluoxetine from increasing them. So we asked whether fluoxetine retained its ability to stimulate progenitor mitosis. Since fluoxetine no longer stimulated progenitor mitosis after a CA3 lesion, we wanted to know whether we could determine more precisely how this happened. It is known that BDNF is increased by fluoxetine, and that this seems essential for increased progenitor mitosis. Double-staining showed that a number of NeuN-expressing cells also stained for BDNF. CA3 lesions themselves had no effect on BDNF in the dentate gyrus after 14 days in experiment 4. Fluoxetine, as expected, increased BDNF expression following 14 days fluoxetine treatment in both controllesioned rats and on the unlesioned side in those with a CA3 lesion. However, it also increased BDNF on the lesioned side, and there was no difference between the two sides . Since increases in both pCREB and Wnt3a expression in the dentate gyrus accompany fluoxetine-stimulated progenitor mitosis, we next asked whether this still occurred after a CA3 lesion As expected, fluoxetine treatment for 14 days increased the expression of both in control rats and on the unlesioned side but there was no difference between the lesioned and non-lesioned sides . Fluoxetine has been reported to decrease the maturation of newly-formed neurons as defined by their expression of calbindin. We confirmed that, on the non-lesioned side, fluoxetine reduced the number of calbindin-positive cells. However, this still occurred on the CA3-lesioned side and there was no difference between them.