TRH responsiveness was investigated in twenty-four males (aged 66-83 years) undergoing stilboesterol therapy for carcinoma of the prostrate. Twelve were taking 2-6 mg daily by mouth for periods of 5 days to 12 months (mean 5 months) (Group A) and the remainder were on daily i.v. doses of 250-500 mg for periods of 3-10 days (mean 8 days) (Group B). In the former group TRH responsiveness was enhanced compared to age matched controls. A contrary effect was observed in the latter group in that the group mean TRH response was significantly lower than that of Group A or of the control group. Basal serum TSH values were unchanged in Group A compared to controls, but a significant elevation in the basal mean value was observed in Group B. The mechanism of action of stilboesterol in the subjects studied remains to be elucidated. Our data are in keeping with either a hypothalamic or pituitary locus for such actions.