When macrometastases are delineated clearly using current radiographic techniques and/or physical examination and can be shown to concentrate 131I, the therapeutic activity to be administered may be determined quantitatively. Administrations of 131I that will deliver 30,000 rad to residual thyroid tissue or 10,000 +/- 2,000 rad to lymph node metastases will ablate them successfully 80% of the time, and bone marrow depression that is severe enough to require specialized treatment will be avoided if the whole blood dose from a single administration does not exceed 200 rad. When micrometastases are detected only by diagnostic radioiodine imaging and/or elevations of serum thyroglobulin levels, and when a clinical decision is made to treat them with radioiodine, then 131I may not be the isotope choice. With small lesions < 0.05 mm in diameter, the lower energy emissions of 125I therapy may be more suitable. With the advent of alternative methods of patient preparation for radioiodine therapy, empiric approaches that were derived from experience with endogenously hypothyroid patients will require full re-evaluation. Approaches based on quantitative radiodosimetric calculations will continue to be valid because they already consider individual differences in radioiodine kinetics.