The role of hypothalamic paraventricular nucleus (PVN) in nociception was investigated in the rat. Electrical stimulation of the PVN increased pain threshold, and microinjection of L-glutamate sodium into the PVN also elevated pain threshold in a dose-dependent manner, whereas cauterization of the PVN decreased pain threshold. Stimulation or cauterization of the area located within 1.0 mm of the outer perimeter of the PVN did not change pain threshold. Pituitary removal could not influence the effect of L-glutamate sodium microinjection into PVN-induced pain threshold increase. The data suggest that PVN plays a role in antinociception through the central nervous system rather than peripheral organs.