The pathogenesis of the Shigella-associated neurological symptoms is unclear. We examined the potential role of host factors. Sonicates of Shigella strains isolated from children with and without neurologic disturbances were compared regarding their ability to induce tumor necrosis factor (TNF) and nitric oxide (NO) in vitro, in mouse macrophage J744 cell line. The mean concentrations of TNF (14.6 vs. 4.4 ng/ml) and NO (7.4 vs. 3.7 microM) induced were higher in response to strains isolated from children with neurologic complications; the differences were not statistically significant. TNF was also measured in plasma of children with shigellosis, and was found to be elevated in all patients. The mean concentration of TNF in plasma of children with neurologic manifestations was higher than that of children with no neurologic symptoms (450 vs. 138 pg/ml, P <0.05). It is concluded that TNF and NO may play a role in the development of neurologic manifestations of shigellosis.