The continuing absence of an identifiable physical cause for disorders such as chronic low back pain, atypical facial pain, or fibromyalgia, is a source of ongoing controversy and frustration among pain physicians and researchers. Aberrant cerebral activity is widely believed to be involved in such disorders, but formal demonstration of the brain independently generating painful experiences is lacking. Here we identify brain areas directly involved in the generation of pain using hypnotic suggestion to create an experience of pain in the absence of any noxious stimulus. In contrast with imagined pain, functional magnetic resonance imaging (fMRI) revealed significant changes during this hypnotically induced (HI) pain experience within the thalamus and anterior cingulate (ACC), insula, prefrontal, and parietal cortices. These findings compare well with the activation patterns during pain from nociceptive sources and provide the first direct experimental evidence in humans linking specific neural activity with the immediate generation of a pain experience.