Expression of the proto-oncogene zif/268 was investigated by in situ hybridization in the hippocampus and cerebral cortex of nerve growth factor (NGF)-transgenic mice during pentylenetetrazol (PTZ)-induced seizures. NGF-transgenic mice displayed normal basal levels of zif/268 mRNA in cortex and hippocampal formation except for the dentate gyrus which contained significantly reduced levels. PTZ induced a similar transient increase of zif/268 mRNA in cortex and Ammon's horn of normal and NGF-transgenic mice. On the other hand, increase of zif/268 mRNA in the dentate gyrus was significantly lower in transgenic mice. Reduced PTZ-induced activation of zif268 may reflect a decreased sensitivity of NGF-transgenic animals to epilepsy by direct or indirect interaction of NGF with immediate early genes.