The effect of scurvy on metabolism of thyroxine (T4) and triiodothyronine (T3) was investigated. Experimental scurvy was produced in guinea pigs by feeding a diet low in vitamin C for 3 or 4 weeks. Control animals received the same diet and ascorbic acid injections. Deiodination of both thyroid hormones was greatly increased in scorbutic guinea pigs. This was shown by an increasing excretion of 131I in the urine and a decreasing retention of protein bound 131I in the plasma, liver and kidney after a single injection of 131I-labeled T4. Similar effects were observed after 131I-labeled T3 injection. Administration of nonradioactive T4 or cortisone to scorbutic animals failed to show any significant changes in the metabolism of 131I-labeled T4. Normal deiodinating activity was completely restored by daily injection of 15 mg of ascorbic acid for 7 days. Scurvy had no effect on the thyroid uptake of 131I in vivo, but increased the amount of 131I-labeled T3 to the erythrocyte in vitro. Both plasma protein-bound iodine and thyroxine levels were significantly decreased in scorbutic guinea pigs. These low values are probably due to a decrease of plasma protein binding capacity during scurvy.