The TSH and T3 response to synthetic TRH was evaluated in 4 groups of patients: normal controls and goitrous subjects from the urban area of Sao Paulo (urinary iodine excretion: 172.2 +/- 48.3 mug I/g creatinine) and nongoitrous and goitrous subjects from the endemic areas of Sao Bento (urinary iodine excretion: 53.8 +/- 17.1 mug I/g). Plasma T4 and T3 were within our normal range in all groups of patients. The mean plasma TSH was significantly higher (5.2 +/- 3.3 muU/ml) in goitrous subjects living in Sao Bento as compared to normal control groups both in urban or endemic areas, and after TRH these patients had an exaggerated and sustained TSH response with a significantly higher peak level (21.1 +/- 7.9 muU/ml). T3 concentration rose in all subjects following TRH and all patients from the Sao Bento endemic areas had a significantly higher proportionate increase in plasma T3 at 120 min. After an injection of iodized oil basal plasma TSH returned to the normal range in the goitrous subjects from Sao Bento. The mean peak TSH response to TRH was 9.1 +/- 3.8 muU/ml at 3 months after the iodized oil injection, and only at 6 months after the iodized oil TSH response was significantly reduced (peak level: 6.1 +/- 2.4 muU/ml). It is confirmed that plasma TSH levels are increased in endemic goitrous patients but not in normal controls living in the same endemic area and it is suggested that the pituitary threshold for inhibition of secretion of TSH by T4 and T3 has been reset in these goitrous subjects to achieve a persistently higher secretion rate of TSH.