Orbital lymphocytic infiltration in thyroid eye disease (TED), as well as identification of somatostatin (SMS) receptors on activated lymphocytes, has provided a rationale for receptor imaging with the radiolabeled SMS analog Pentetreotide. In 80 patients with TED, single-photon emission computed tomography (SPECT) images of the orbit were performed 4 and 24 hours after injection of Pentetreotide. Semiquantitative evaluation was performed using the SPECT slices with irregular regions of interests placed over the orbits and both hemispheres. In contrast to controls (median 5 counts per voxel per millibecquerel (cts/vox/MBq) injected activity), TED patients showed threefold increased orbital accumulation of Pentetreotide (15 cts/vox/MBq, p = 0.003). When considering patients with active TED only, even higher uptake was registered (23 cts/vox/MBq, p = 0.0006 vs. controls, sensitivity for active TED 61/68, 90%; specificity 12/12, 100%). In 40 patients with active TED, the radionuclide accumulation decreased sharply after completion of immunosuppressive therapy. A high pretreatment Pentetreotide orbit-to-brain ratio correlated with a response to therapy (positive and negative predictive values 28/32, 88%, and 8/8, 100%, respectively). In conclusion, SMS receptor scintigraphy may be regarded as a semiobjective tool in the evaluation of TED, both at initial stages as well as during treatment.