Purpose The authors evaluated the utility of Tc-99m-labeled human immunglobulin G (HIG) in determining the severity of orbital inflammation and the relation of orbital Tc-99m HIG uptake and clinical parameters in patients with Graves' ophthalmopathy. Materials and methods Images were obtained in 23 patients (13 women, 10 men; mean age, 51+/-10 years) with Graves' ophthalmopathy. Planar orbital images were obtained and SPECT was performed using a triple-detector gamma camera 4 hours after 370 MBq (10 mCi) Tc-99m HIG injection. Tc-99m HIG uptake was classified using transaxial and coronal slices as 1, mild; 2, moderate; and 3, severe. The clinical severity of orbital disease was categorized, according to the criteria described by Feldon and Unsold, as class I, mild involvement; class II, moderate; and class III, severe. Disease was considered to be clinically inactive if symptoms and signs were stable or improved in the last two examinations performed at least 6 months apart. Results Sixteen patients were clinically inactive, and seven patients were active. The mean Tc-99m HIG classes were 1.5+/-0.5 and 2.6+/-0.5, respectively (P = 0.02). There was not a good correlation between the clinical classification and Tc-99m HIG classification, whereas the presence of active disease showed a good correlation with Tc-99m HIG classification (r = 0.703; P = 0.0002). Conclusions Tc-99m HIG imaging showed possible ongoing subclinical inflammation in the orbits of the patients with Graves' ophthalmopathy regardless of the clinical classification. Tc-99m HIG SPECT seems a promising procedure for evaluating the presence of active orbital inflammation.