In order to clarify the involvement of substance P (SP) and neurotensin (NT) neurons in the response of organisms to stress, SP-like immunoreactivity (SP-LI) and NT-like immunoreactivity (NT-LI) were determined in various regions of the rat brain following exposure to the whole-body vibration (20 Hz, 4 G, 90 min). SP-LI and NT-LI in the rat brain were measured by means of a sensitive and specific double-antibody solid-phase enzyme immunoassay. SP-LI in the frontal cortex was significantly reduced following whole-body vibration, while that in the nucleus accumbens and amygdala was significantly increased. NT-LI in both the frontal cortex and the hypothalamus of rats exposed to the whole-body vibration was significantly increased. However, striatal SP-LI and NT-LI remained unchanged. The present findings indicate that the SP and NT neuronal systems in various brain areas are involved in the response to stress. The frontal and amygdalofugal SP and hypothalamic NT neuronal systems, in particular, may have an important role in mediating the response of organisms to the whole-body vibration-induced stress.