Male rats of a final weight 350-400 g were fed low iodine diet for 4 weeks and injected radioiodide for 6 days prior to the experiment. They were anesthetized with pentobarbiturate and external arteriovenous shunt was made with the aid of thin polyethylene tubing to collect frequent blood samples while maintaining isovolemia as previously described. The injection of 20 mug synthetic TRH into carotic artery in rostral direction resulted in an increase of plasma thyroxine radioactivity showing a maximum at 120 min after the injection. This increase was prevented with the aid of i.v. injection 20 mug L-thyroxine at 20-180 min before TRH administration. Moreover, the preventive effect of thyroxine was completely blocked by the i.v. injection of actinomycin D (0.8 mg/kg) 60 min before thyroxine, while the administration of cycloheximide (4 mg/kg), at the same time, was without effect. The mechanism of this phenomenon remains to be further elucidated.