This study was conducted to assess the influence of dopamine on thyrotropin secretion in patients with primary hypothyroidism before and after optimized L-thyroxin replacement therapy. Thyrotropin responses to dopamine infusion (4 microg/kg/min over 3 hours) and IV metoclopramide (10 mg bolus), a dopamine receptor blocker were studied in 25 consecutive patients with primary hypothyroidism before and after achieving stable euthyroid state and compared with 15 normal age-matched controls. Thyrotropin response to both dopamine infusion (decremental) and IV metoclopramide bolus (incremental) was greater in patients with primary hypothyroidism than that in the control subjects. Thyrotropin response was greater in women than in men. The magnitude of decremental thyrotropin response to dopamine infusion and the incremental response to IV metoclopramide bolus significantly correlated with the basal T3 and T4 levels. Thyrotropin response was blunted to dopamine infusion but not to metoclopramide at follow-up after six-month replacement with L-thyroxin, and both the responses were comparable in women and men in patient group. We conclude that modulation of dopaminergic system by dopamine or by dopamine receptor blocker has a greater influence on thyrotropin secretion in patients with primary hypothyroidism than euthyroid normal subjects.