To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT). The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain. Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased. The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls. The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.