There was a marked reduction by visual inspection of GAP-43 within the granule cells on the side of a CA3 lesion compared to the non-lesioned side. This paper shows that lesions of the hippocampal CA3 have major effects on neurogenesis in the dentate gyrus. This has never been reported before. Since we have not explored the effects of lesions in other CA fields, we cannot be sure at this stage that these results are specific to CA3, though, because of the particular relation between this field and the dentate gyrus, it seems likely that they will prove to be so. Our first finding was that basal levels of progenitor cell mitosis were not altered by a CA3 lesion, but the dentate gyrus was seemingly unable to respond to a wellestablished treatment – fluoxetine – that increases it. Since effects on basal or stimulated rates of mitosis may differ, it is important to define ‘basal’ levels. This is always problematic, particularly in the case of hippocampal neurogenesis which is so sensitive to a variety of environmental influences. In particular, perturbations of adrenocortical activity can easily alter rates of neurogenesis. However, the rats we used were wellaccustomed to their standardised housing and social environment, so could be credibly classified as being in a ‘basal’ state. Both our first experiment, in which we measured Ki-67-labelled cells, and the fourth one, where we gave BrdU up to 24 hours before sacrifice, confirmed that CA3 lesions had no effect on basal levels of progenitor mitosis. However, we found that fluoxetine was no longer able to increase the mitotoic rate of progenitor cells in the dentate gyrus in the presence of a CA3 lesion. Reports on the ability of this drug to stimulate mitosis have differed. Some confirm a positive result but others do not. Emerging evidence suggests that route of administration is important: only minipump infusions have reliably increased mitosis rates. The solvent used is another factor: propylene glycol itself increases mitosis rates. Our finding that there are differential effects of a treatment on stimulated progenitor cell mitosis, but not basal levels, echoes previous reports. We find, for example, that blocking trkB receptors with the drug K252a has no effect on basal mitosis rates, but prevents the increase which otherwise follows treatment with fluoxetine. This suggests that particular mechanisms are involved in raising mitosis rates in response to modifications in serotonin activity. This is not because basal levels cannot be reduced: treatment with excess corticoids suppresses mitosis to well below the basal rate. Previous results have also shown that BDNF is involved in the response to progenitor cell to fluoxetine. We therefore sought to determine whether the expected increase in BDNF content in the dentate gyrus following fluoxetine treatment might have been prevented by CA3 lesions. But this was not the case. The anticipated increase in BDNF following changed serotonin still LY2109761 occurred.