The effect of Fusaric acid (FA), a specific inhibitor of dopamine beta-hydroxylase, on humna TSH and thyroid hormone concentration (T4 and T3) was evaluated. Healthy subjects showed no significant changes in serum T3,T4 and TSH concentrations following the administration of FA calcium salt (FA-Ca) or placebo. Similarly, administration of FA-Ca for 4 weeks to hypertensive patients failed to produce significant changes in the serum T4 or T3 Resin Sponge Uptake values, and in the TSH and T3 responses to TRH. In contrast, FA-Ca produced a significant reduction on the high basal serum TSH level in patients with primary hypothyroidism. The mean nadir was 25% and ranged from 6 to 61%. As in the case of L-Dopa, the effect of FA-Ca on serum TSH is most clearly demonstrated in patients with primary hypothyroidism. Alterations in brain amines may directly or indirectly suppress pituitary TSH secretion. The possibility of changes in the peripheral distribution or turnover rate of TSH has not been excluded.