A tissue-specific dosimetric method based on gamma camera acquisitions was developed to determine the 131I activity to administer to patients with autonomous thyroid nodules (ATN) to deliver 200 Gy to the nodule and to evaluate the correspondent dose to extranodular tissue. Twenty patients with ATN were given 111 MBq of 123I i.v. and their neck was imaged 2, 4, 24, 48, and 120 hours after administration to evaluate separate iodine kinetics for nodule and contralateral lobe. The volumes of nodule and lobe were measured on the 4 hour scintigraphic image, after optimization of the method on a thyroid phantom. Three simplified dosimetric methods were then considered and compared to the reference method in terms of 131I activity: (a) three point method, based on 4, 24, and 120 h acquisitions, (b) fixed T1/2 method, that measures only the 24 h uptake and assumes an effective half-life of 5 days for the nodule, (c) fixed activity method, based on the administration of 413 MBq of 131I. The mean 131I activity to administer to the 20 patients was 413 MBq (range 65-1327) and the mean dose to the contralateral lobe was 43 Gy (range 11-121). The percentage differences in 131I activity between the reference method and the simplified methods were in the ranges: (a) -14%, 13%, (b) -42%, 74%, (c) -69%, 533%. The relevant dose to extranodular tissue and the great interpatient variability of the radioiodine activity required to give a predetermined dose to ATN suggest that a tissue specific dosimetric approach based on gamma camera acquisitions is fundamental. A simple method based on only three uptake measurements is a reliable alternative to the five point method when the clinical workload of a Nuclear Medicine department is particularly heavy.