The follow-up of 15 patients with differentiated cancer of the thyroid was analysed retrospectively. All patients had persistent or developed elevated thyroglobulin (Tg) plasma levels (greater than 10 ng/ml) after total thyroidectomy and 131 I therapy. There was no evidence of thyroid remnants or metastases in the 131 I whole body scan, bone scan, chest X-ray or clinical investigation. Nine of 15 patients developed local or distant metastases during a follow-up period of 3-39 months (mean = 18 months). Only one of seven recurrences tested were 131 I positive, Tg values of 9 from 12 patients showed no correlation to the Thyroid-stimulating hormone (TSH) level. It is concluded that: (1) this group of patients is at high risk of developing a recurrence (2) new methods have to be developed for the localization of 131 I negative but Tg positive metastases.