Thyroliberin (TRH) has been reported to be synthesized in anterior pituitary. Modulations of anterior pituitary concentrations of TRH and its precursor (proTRH) were investigated in rats rendered hypothyroid for 21 and 48 days. In hypothyroid rats, as expected, plasma TSH levels were increased and plasma free T4 concentrations were reduced, whereas anterior pituitary concentrations of TRH were markedly increased (mean +/- SEM fmol/mg protein, 106.9 +/- 21.1 at 21 days and 181.8 +/- 59.0 at 48 days vs 42.2 +/- 13.4 in controls). Significant increases of proTRH concentrations were found in hypothyroid rats (mean +/- SEM fmol/mg protein, 266.5 +/- 16.7 at 21 days and 320.4 +/- 51.1 at 48 days vs 214.1 +/- 18.3 in controls). Daily administration of L-T4 for the last week of PTU treatment (days 41 to 48) reversed hypothyroidism by lowering plasma TSH levels and by increasing plasma free T4 concentrations. Concomitantly, T4 administration significantly decreased anterior pituitary TRH contents (114.4 +/- 35.9) as well as proTRH contents (250.4 +/- 11.7). The fact that hypothyroidism regulates anterior pituitary TRH and proTRH contents strengthens the view that TRH might play a role in local regulatory mechanisms within the anterior pituitary on the thyrotropic function.