SUMMARYThyroglobulin (Tg) is secreted only by the thyroid gland and its presence in serum should therefore indicate the presence of functioning thyroid tissue. We have measured Tg in cord and heelprick serum samples from 230 newborn infants with no thyroid disease and in forty‐seven infants with suspected neonatal hypothyroidism. In the euthyroid group, well full‐term infants showed an increase in Tg post‐natally which was not seen in ill full‐term or pre‐term neonates. Thyroid hormones were lower and TSH higher in the ill and pre‐term groups, which, in conjunction with the lack of increase in Tg, suggests impaired thyroid secretion in these groups.Of the forty‐seven hypothyroid infants (low T4 with raised TSH) thirty‐five had measurable Tg; twenty‐eight of these had thyroid scans, and twenty‐seven showed the presence of thyroid tissue. Of twelve infants without measurable Tg seven were scanned; four showed no thyroid uptake, in the other three thyroid tissue was demonstrable; two of these had a positive family history of goitrous hypothyroidism.It appears that many infants with biochemical hypothyroidism (low T4 and high TSH) have functioning thyroid tissue (measurable Tg and positive scan). Adequate thyroid hormone replacement therapy should be instituted in all cases, but assessment of therapy at a later stage of childhood may establish whether the prognosis for the group with functioning thyroid tissue, especially for mental impairment, is different from those without demonstrable thyroid function.