Both direct and indirect environmental stress to the brain can increase the expression of transcription factor c-fos in various populations of neurons. In this study, we examined whether the intraperitoneal injections of lidocaine at doses inducing convulsions within 10 min, increased the level of c-fos mRNA and protein in forebrain areas. In in situ hybridization using [35S]UTP-labeled antisense c-fos, cRNA increased c-fos mRNA levels through the hippocampal formation, piriform cortex, septum, caudate-putamen, neostriatum, and amygdala within 2 hr. In parallel with the mRNA expression, c-fos protein immuno-reactivity was also observed in the same forebrain areas. In contrast to the seizure activity and wide-spread neuronal degeneration following kainate treatment, injections of lidocaine did not produce neuronal death within three days. The present study indicates that lidocaine induces convulsions and c-fos expression without causing neurotoxicity.