Serum thyroglobulin (Tg) measurements were performed in 17 children with congenital hypothyroidism due to an ectopic thyroid gland before therapy and during follow-up. Data were analysed in four periods according to duration of therapy and compared to results obtained in a group of 51 normal children aged 1 month to 6 yr. At diagnosis serum Tg was higher than the mean normal value measured at a similar age. We observed a rapid and parallel decrease of both Tg and thyroid-stimulating hormone during the early weeks of therapy. However, Tg was always detectable in the serum of treated (euthyroid) patients. After 34 months of therapy serum Tg was 11.4 +/- 1 ng/ml, a value significantly different (p less than 0.001) from that obtained in normal controls of similar age (23.5 +/- 3 ng/ml). In nine treated children aged more than 2 yr, thyroid-stimulating hormone and Tg were increased after a brief period of decreased L-thyroxine dosage. These data indicate that ectopic thyroid tissue does not involute during thyroxine therapy and, in response to elevations of serum thyroid-stimulating hormone, can be stimulated to secrete Tg.