The p75 neurotrophin receptor has been implicated in the regulation of multiple cellular functions that differ depending on the cell context. We have observed that p75^NTR is strongly induced on astrocytes as well as neurons in the hippocampal CA3 region after seizures; however, the function of this receptor on these glial cells has not been defined. We have employed a primary culture system to investigate the effects of neurotrophins on astrocytes. Treatment of hippocampal astrocytes with nerve growth factor (NGF) caused a reduction in cell number, but did not elicit an apoptotic response, in contrast to hippocampal neurons. Instead, activation of p75^NTR by NGF attenuated proliferation induced by mitogens such as EGF or serum. These studies demonstrate the cell type specificity of neurotrophin functions in the brain. © 2009 Wiley‐Liss, Inc.