Electrical stimulation of the brain can produce a selective and potent modulation of responding to noxious stimuli in animals and man. The influence of various stimulation parameters is discussed. Brain stimulation at numerous loci results in analgesia. The most well characterized regions are the mesencephalic periaqueductal gray matter and the medullary raphe nuclei. One pain inhibitory system activated by brain stimulation involves a neural circuit from the PAG to the medullary raphe nuclei. Output from there descends via the DLF to modulate pain transmission in the dorsal horn of the spinal cord. Other analgesia systems are also activated by brain stimulation. Compelling evidence implicates endogenous opiates in SPA. Monoaminergic neurotransmitters are also involved in SPA. Brain stimulation has proven to be useful for the management of some forms of intractable pain in man.