Plasma TSH responses after an i.v. injection of 100 mg of L-dopa were evaluated by radioimmunoassay in 4 normal euthyroid subjects and in 8 patients with primary hypothyroidism. In agreement with previous results, no variations in plasma TSH levels were observed in the euthyroid subjects. In contrast, in primary hypothyroidism L-dopa induced a biphasic response in plasma TSH. In fact, we observed a transitory increase with a maximum at 30 min (mean ± SEM = 54 ± 18%) followed by a decrease reaching a minimum level of plasma TSH basal values at 90 min (mean ± SEM = 15 ± 6%). These findings demonstrate that the plasma TSH response to L-dopa in primary hypothyroidism is time-dependent. Some speculation on the possible mechanism of this action is presented.