A study of changes in serum T4, T3, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean +/- s.e.m. serum T4 (21.6 +/- 8.2 micrograms/dl), T3 (315 +/- 191 ng/dl) and Tg (149 +/- 52 ng/ml) concentrations were significantly higher than in normal subjects (8.5 +/- 1.7 micrograms/dl, 136 +/- 34 ng/dl, and 10.5 +/- 1.0 ng/ml, respectively). The basal TSH concentrations failed to increase in response to TRH. Mean serum T3 and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. However, normalization of clinical status and serum thyroid hormone levels did not coincide with the normalization of serum Tg levels. Thyroid autoantibodies were absent during the whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T3 to T4 ratio above the normal range (7-24 ng/micrograms) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.