The effect of arginine on serum prolactin concentrations was studied in 18 normal subjects and in 7 patients with hyperthyroidism in normal subjects, arginine infusion produced an increase of serum prolactin at least 6 ng/ml from the baseline, and the mean peak level (25.2 +/- 3.3 ng/ml, mean +/- SE) was significantly higher than the basal level (8.6 +/- 5.2 ng/ml, P less than 0.001). There was no significant difference in the peak levels between sexes. Unlike prolactin, concomitant serum thyrotropin levels did not change after the arginine infusion. In hyperthyroid patients, the increment of serum prolactin after arginine infusion at 30 min (3.9 +/- 1.5 ng/ml) was significantly lower than that of the normal controls which were matched by age and sex (17.1 +/- 4.4 ng/ml, P less than 0.05). After treatment when these patients were euthyroid, the increment of prolactin after arginine infusion at 30 min was significantly increased (16.3 +/- 4.3 ng/ml, P less than 0.05) and had reached the level of control subjects. These data indicate that the prolactin response to arginine in hyperthyroidism is diminished.