The aim of the present study was to investigate the possible role of hydrogen sulfide (H2S) in the pathogenesis of recurrent febrile seizures (FS) in rats. On a rat model of recurrent FS. the ultrastructure of hippocampal neurons, the plasma level of H2S, the expressions of cystathionine b-synthase (CBS) and c-fos, and the development of mossy fiber sprouting (MFS) in hippocampus were examined after treatment with NaHS, a donor of H2S, or hydroxylamine (HA), an inhibitor of CBS. We found that the pi-sina level of H,S increased significantly, the expressions of CBS and c-fos increased markedly. and MFS was evident in hippocampus in FS group. NaHS alleviated the neuronal damage of recurrent FS rats. decreased the expression of c-fos, and inhibited MFS obviously. HA aggravated the neuronal damage of recurrent FS rats. further increased the expression of c-fos, and enhanced the mossy fiber outgrowth. The results showed that endogenous H2S system was involved in the development of FS. Exogenous H2S may exert beneficial effect on the pathogenesis of FS-related brain danage. (C) 2004 Elsevier Inc. All rights reserved.