Infants with athyrotic hypothyroidism usually manifest signs and symptoms of hypothyroidism prior to or during the period in the newborn nursery. These features are variable and include: prolonged gestation with large size at birth, large posterior fontanel, respiratory distress, hypothermia, peripheral cyanosis, hypoactivity, poor feeding, lag in onset of stooling, abdominal distension with vomiting, protracted icterus, and/or edema. Retrospective assessment of newborn nursery records of three infants from the Collaborative Perinatal Project who were subsequently found to have congenital hypothyroidism disclosed that they had six, eight, and nine, respectively, of these features while in the newborn nursery. Evaluation of newborn records on 12 other infants, often less complete, who were later found to have congenital hypothyroidism disclosed that each infant had from one to seven of these signs and symptoms, with an average of 3.2 per infant. Thus the most important period for clinical consideration of athyrotic hypothyroidism is in the newborn nursery to initiate early thyroid replacement therapy in affected infants.