A sensitive radioimmunoassay for the measurement of TSH in the eluate of blood spotted on filter paper has been developed. The method is consistently sensitive to 0.1 to 0.25 muU of TSH and enables the detection of values equivalent to 6 to 15 muU/ml of serum. The measurement of TSH in the filter paper spot in all infants with low filter paper spot T4 has permitted rapid confirmation of 10 cases of neonatal hypothyroidism. However, cases of hypothalamic hypothyroidism with low or normal filter paper spot TSH concentrations would have been missed using only this method. Since these patients represent approximately 10% of our neonatal hypothyroid population, we do not recommend this method as a primary screening procedure, but rather as a confirmatory test which will accelerate the diagnosis and therefore the onset of therapy.