Rats were injected with [125I]L-thyroxine (T4) ip 16 h before the experiment and samples of blood were frequently taken from polyethylene tubing inserted into the femoral artery in anaesthetized and heparin injected animals, isovolaemia being maintained. In each sample of plasma T4 counts per ml were estimated with the aid of paper chromatography. Rapid decrease of circulating T4 level was found at 20 min after iv injection of various compounds (thiocyanate, iodide, fluoroborate, theophylline and salicylate) and a dose-response relationship was established between such a decrease and the administered dose of salicylate (5-160 mg/400 g b.w.). A similar decrease was observed at 60 min after ip injection of some general anaesthetics (thio-, pento- and allo-barbiturate, urethane) or tranquilizers (Innovar-Vet). Finally, an incrase of T4 fractional disposal rate was found between 120 and 480 min after the administration of some of the above mentioned anaesthetics and this effect was abolished by the administration of thiocyanate. It was concluded that there are two different effects of drugs on the circulating T4 level: 1. the immediate effect resulting apparently from a decreased plasma protein binding; 2. the prolonged effect which presumably results from the increased turnover of T4 by peripheral tissues, the metabolic basis of which remains unexplained.