The amygdala is known to regulate neuroendocrine and behavioral responses to a variety of stimuli. Herpes simplex virus-1 (HSV-1) is the common cause of viral encephalitis, manifested by hypothalamic-pituitary-adrenal (HPA) axis activation, fever, hypermotor activity and aggression. We examined here the role of the central amygdala (cAMG) in regulating the HPA axis function, febrile and behavioral responses to HSV-1 infection in rats. Bilateral electrolytic lesions were performed in the cAMG. HSV-1 encephalitis was induced by intracerebroventricular (ICV) inoculation of purified virions. Motor activity and body temperature were examined by a biotelemetric system. ICV inoculation of HSV-1 caused a marked time-dependent increase in serum corticotropin (ACTH) and corticosterone at 4 and 24 h post-infection. These responses were attenuated in rats with bilateral lesions of the cAMG. HSV-1 infection induced fever, motor hyperactivity and aggressive behavior. These responses were also attenuated in rats with cAMG lesions. The cAMG plays an important role in mediating the neuroendocrine, febrile and behavioral responses to HSV-1 infection.