It is well known that the pituitary PRL secretion is modified in patients with primary hypothyroidism. The serum PRL is elevated in approximately one third of patients, the others presenting with enhanced PRL release after TRH intravenous (i.v.) administration. The objective of this study was to verify how treatment with L-thyroxine modifies the enhanced PRL response to TRH administration in a group of patients with primary hypothyroidism. Eight female patients aged 28 to 64 (mean age +/- SD = 17.2 +/- 6.0) with primary hypothyroidism were studied. Diagnosis was based on clinical features and plasma FT4 (mean +/- SD = 5.2 +/- 0.9 pmol/l; n.r. 7.7-19.3 pmol/l) and TSH (mean +/- SD = 87.3 +/- 20 mUI/l; n.r. 0.2-5 mUI/l) levels. As controls eleven normal age-matched female subjects were also studied. After an overnight fasting an indwelling catheter was inserted into an antecubital vein of the forearm and kept patient by slow infusion of normal saline solution. After 60' the basal blood sample was collected and 200 mcg of TRH was injected intravenously (0'), further blood samples were taken at 30', 60', 90', 120' and 180'. PRL determinations (n.r. 3-19 ng/ml) of the blood samples obtained were made using fluoroimmunometric assay. Hypothyroid patients underwent a second TRH test after L-thyroxine replacement therapy (100 mcg/day) had led to euthyroidism for at least three months.(ABSTRACT TRUNCATED AT 250 WORDS)