During development, neuronal circuitry and memory formation are associated with the synthesis and release of several biological mediators, including cytokines. Among the numerous cytokines, the role of tumor necrosis factor-alpha (TNF-alpha) in neurobehavioral development is largely unknown. Thus, the recently generated transgenic mice expressing murine TNF-alpha in the brain represent a valid animal model for investigating the role of TNF-alpha in neurobehavioral processes. Using these mice, we showed that an overexpression of murine TNF-alpha increases grooming in the novel object investigation test, decreases rearing as a reaction to novel olfactory cues, and produces a retardation of passive avoidance acquisition while enhancing the thermal response in the hot-plate test, a task regulated by both peripheral and central mechanisms. The possibility that these effects are associated with endogenous changes in concentration of the NGF, known to be modulated by TNF-alpha, is discussed.