Total and free thyroid hormones (T3, T4, FT3, FT4), TSH and PRL were determined in basal conditions and after stimulation with TRH in 32 patients affected by autonomous thyroid nodules before and after nodulectomy and in 24 control subjects. Only 7 patients were clinically thyrotoxic and thyroid hormone concentrations were slightly elevated in most cases. In untreated patients the increment (delta) in PRL after TRH was significantly lower than in normal subjects but was not as severely depressed as that of TSH. After nodulectomy both delta PRL and delta TSH increased and were not significantly different from those found in normal subjects. Thus PRL responsiveness to TRH is depressed by prolonged though moderate increases in thyroid hormone concentrations but is not as sensitive to their action as TSH.