SUMMARYShort‐term fasting in humans is associated with diminished Δ TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 μU/ml; normal range 0.66‐2.98 μU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide‐treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 ± 0.3 μU/ml (mean ± SEM) in the fed state and increased to 14.7 ± 3.5 μU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 ± 0.3 μU/ml was significantly decreased (P<0.01) compared to control, as was the level of 8.8 ± 2.3 μU/ml (P<0.01) obtained 20 min after TRH. In the iodide‐treated group the basal TSH level was 1.4 ± 0.2 μU/ml during feeding which increased (P<0.025) to 2.9 ± 0.7 μU/ml during fasting; the TSH value 20 min after TRH was 12.6 ± 2.5 μU/ml while feeding and 17.3 ± 2.9 μU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups. That free T4 (pmol/l) rose significantly during fasting (28.7 ± 1.3 vs 33.8 ± 1.3,P<0.01) in the control group but was unaltered in the iodide‐treated group (23.8 ± 1.3 vs 26.2 ± 2.5) suggests an aetiological role for free T4 in blunting TSH responsiveness. The abolition by iodide of the fasting‐related changes in TSH further suggests that normal pituitary feedback regu