To determine if subacute thyroiditis (SAT) is associated with changes in the regional perfusion of the thyroid gland, we performed Tc-99 m sestamibi scans on eleven patients with SAT who had painful goiter and clinical thyrotoxicosis. Eleven patients had Tc-99 m pertechnetate and Tc-99 m sestamibi scintigraphy during the acute stage of SAT. The thyroid uptake ratio of sestamibi was compared with the laboratory data and color Doppler ultrasonography. Tc-99 m pertechnetate scintigraphy in the thyroid was markedly reduced during the acute stage of SAT. Conversely, Tc-99 m sestamibi showed diffuse increased uptake in the thyroid region, suggesting increased perfusion. On the other hand, there was near absence of vascularization in the acute phase and slight increase in the recovery phase by color Doppler ultrasonography. The clearance rate of Tc-99 m sestamibi during the early phase (from 10 min to 1 h) was decreased in the acute stage of SAT. The sestamibi uptake ratio correlated with serum immunosuppressive acidic protein (IAP) in the acute stage of SAT and the sestamibi uptake ratio in the recovery stage of SAT was correlated with serum thyrotropin levels. Tc-99 m sestamibi uptake in the early phase in the acute stage of SAT may reflect the inflammatory process associated with SAT.