Synthetic thyrotropin-releasing hormone (TRH) has been shown to be a stimulator of prolactin release as well as of thyrotropin (TSH) release in normal man. This paper presents data concerning the effect of TRH on the PRL response in normal human subjects and in patients with thyroid diseases. Synthetic TRH (500 mug) was administered intravenously to 12 normal males, 12 normal females, 8 female patients with hyperthyroidism, and 8 female patients with primary hypothyroidism. Blood samples were taken for the determination of the serum prolactin(PRL) and thyrotropin (TSH concentrations. Serum PRL and TSH levels were determined by each specific and sensitive radioimmunoassay. The mean serum PRL level was 6.1 +/- 4.9 ng/ml (mean +/- SD) before TRH administration in normal females, and 4.9 +/- 5.0 ng/ml in normal males. The difference was not statistically significant. The serum PRL levels 15 min after TRH administration were significantly higher in females than in males (42.0 +/- 17.2 vs. 26.3 +/- 8.6 ng/ml, p smaller than 0.001). The mean serum PRL level before Trh administration in patients with hyperthyroidism was higher than in normal females (12.5 +/- 5.5 vs. 6.2 +/- 4.9 ng/ml, p smaller than 0.05), but the mean serum PRL level 30 min after TRH was lower in cases of hyperthyroidism than in normal females (14.3 +/- 5.0 vs. 44.1 +/- 13.7 ng/ml, p smaller than 0.05). The mean serum PRL level before TRH administration in primary hypothyroidism was significantly higher than in normal females (37.6 +/- 29.0 vs. 6.2 +/- 4.9 ng/ml, p smaller than 0.05) and serum PRL level after TRH was also higher in hypothyroidism than in normal females (132.8 +/- 83.4 vs. 42 +/- 17.2, p smaller than 0l05). There was a positive correlation between the maximum increase in serum PRL concentration above the base line (...PRL) and the increment in serum TSH (...TSH) after TRH administration in these subjects. In conclusion, the PRL response to TRH was greater in females than in males, abolished in hyperthyroidism and exaggerated in primary hypothyroidism. These results indicate that the thyroid hormone concentration influences the PRL response to TRH as well as TSH response.