The evidence relating to the site and mechanism of action of "centrally acting" agents which may affect visceral sensitivity is reviewed. Antidepressant drugs such as amitriptyline as well as the newer selective serotonin reuptake inhibitors are thought to act at the level of the CNS. Opiates, including morphine as well as compounds such as trimebutine or fedotozine designed for therapeutic use in irritable bowel syndrome, are effective in reducing visceral nociception. Cytokines in the CNS are known to be involved in the modulation of pain and there is also evidence to suggest that centrally acting cytokines may play a role in the production of visceral hypersensitivity. Consequently, they may provide an interesting target for future research.