Forty-eight premature infants, whose condition seemed satisfactory at one week of age and whose weights approximated 1500 gm., were selected for this study. Even-numbered infants in the series were given daily doses of desiccated thyroid or thyroxin for periods averaging 3½ weeks; odd-numbered infants were given placebos of lactose according to the same schedule. The clinical progress of the infants was noted and weekly red cell counts, hemoglobin and serum protein-bound iodine levels were determined. 1. Daily doses of 60 to 120 mg. thyroid produced no significant effects upon clinical condition and progress or upon the protein-bound iodine level. 2. Daily doses of thyroid 180 mg. or thyroxin 0.2 mg. did not affect the caloric and fluid intake, the gavage incidence, the amount of vomiting, the skin color or the body temperature. Such dosage, however, decreased the weight gain, increased the pulse rate and increased the incidence of diarrhea. A higher percentage of infants so treated required blood transfusions and did not fare so well clinically. The level of serum protein-bound iodine was elevated. The administration of thyroid or thyroxin to premature infants selected as noted above is therefore without observable benefit and is sometimes harmful. The effects of daily dosage with thyroxin 0.2 mg. were at least as great as those with thyroid 180 mg. 3. The mean protein-bound iodine level of 32 untreated infants was 5.7±.47 at an average age of 9 days, and mean values for the control infants did not differ significantly from this figure during a subsequent five week period. These levels do not suggest that the premature infant is deficient in circulating thyroxin. 4. Thyroid doses exceeding 120 mg./day are necessary to produce pharmacologic effects in premature infants and in euthyroid children and adults. This implies that the thyroid gland of the premature infant produces and releases thyroxin in amounts comparable to those of normal, older human beings and approximating 120 mg. thyroid/24 hours. Medication of the athyrotic cretin should be adjusted with this in mind. 5. When caloric intake is adjusted by the desires of the premature infant, he ingests an average of about 150 calories/kg. body weight/24 hours. On such a regimen, his weight gain approximates that of his fetal colleague of the same gestational age and averages more than 30 gm./day.