The effect of 6-propylthiouracil (PTU) on the peripheral conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (reverse T3, rT3) was investigated by assessments of the concentrations of T4, T3, and rT3 in peripheral venous blood from T4-treated healthy volunteers given PTU, 4 × 150 mg daily. Within on day of PTU administration, serum T3 concentrations were reduced, and those of rT3 enhanced. These deviations lasted as long as PTU was given (five days), and there was a rapid return towards normal within one day after PTU administration ceased. It seems probable that, in man, PTU can evoke a diversion of T4 monodeiodination, less being converted to the metabolically active T3 and more to the metabolically inactive rT3. It is possible that the rapidity whereby PTU can reduce T3 levels can offer an advantage in the treatment of hyperthyroidism.