Twenty-five patients with nontoxic nodular goiters and six with toxic goiter were studied prior to subtotal thyroidectomy, with closely spaced blood sampling up to three weeks after surgery, and approximately one year after surgery. Serum thyroglobulin (Tg) was measured by a previously described radioimmunological method. The mean serum Tg was elevated in patients with nontoxic nodular and toxic goiters compared to sex and age matched control groups with pronounced increases during surgery. The disappearance curves of Tg in both groups had two exponentials, an initial steep slope with a half-life of 4.0 +/- 1.8 (SD) h in nontoxic goiter and 4.5 +/- 3.2 h in toxic goiter. This was followed by a more shallow slope with a half-life of 3.6 +/- 1.1 days in nontoxic goiter and 3.4 +/- 0.8 h in toxic goiter, the breaking point between the slopes lying approximately at 48-72 h. There was no significant difference between the half-life of Tg in patients with toxic or nontoxic goiters, respectively. There was a weak correlation between the weight of the removed thyroid tissue and the maximally obtained Tg concentration at the time of surgery, but no correlation with the levels before operation. Serum Tg was significantly lower three weeks after operation and approximately one year after surgery. In conclusion, different forms of the Tg molecules seem to be removed at different rates, independent on the type of goiter.