Five hypothyroid patients are reported with increased pituitary TSH response to TRH during administration of T3. In one patient treated with intravenous T3, 50 micrograms daily for 10 days, the peak serum TSH and total pituitary TSH reserve after TRH increased coincident with increases in serum T3 and T4 levels and a decrease in the basal TSH concentration. In four patients treated with oral T3, the peak serum TSH and total pituitary TSH reserve after TRH increased during administration of subphysiological doses of T3. Peak serum T3 levels occurred 4 h after ingestion and increased progressively with increasing T3 doses. Serum TSH levels decreased modestly with the nadir at 4 h after T3 ingestion and then returned to basal levels at 24 h. Augmentation of TSH responses to TRH occurred simultaneously with decreases in serum cholesterol, as well as increases in the pituitary prolactin response to TRH, and increase in the GH and cortisol response to insulin induced hypoglycaemia where these responses could be studied. These data demonstrated a positive effect of subphysiological T3 therapy in these hypothyroid patients on the TSH response to TRH as well as increases in the responses of other pituitary hormones to stimulation.