Complete turnover studies of T4, T3, rT3, and 3,5,3',5-tetriodothyroacetic acid (TA4) were carried out in normal subjects given T4 (0.2 mg, by mouth daily) by the integration method. When compared to the five fed controls, the four fasting subjects showed a decrease of mean T3 disposal from 41 to 18 micrograms/day, an increase of mean rT3 disposal from 49 to 61 micrograms/day. The mean serum TA4 concentration rose from 53 to 112 ng/dl, while the TA4 metabolic clearance remained unchanged. The fraction of T4 metabolized by deiodination changed from 79.0% to 77.5% in the fasting subjects as the fraction of T4 metabolized by deamination changed from 1.1% to 2.2%. Therefore, fasting induces a significant shunting of T4 away from T3 production into rT3 and TA4 production. However, oxidative deamination remains a minor metabolic pathway of T4 in man during both normal and fasting conditions. Given its low disposal rate and low biological potency, the increased TA4 production during fasting is probably not the inhibitory factor of TSH response to the lowered T3 production during fasting.