We have simultaneously measured T4 and TSH concentrations from 93,000 consecutive filter paper blood samples received by the Quebec network for Genetic Medicine. T4 was measured using the Micromedic Automated System and TSH was measured by RIA kits from Pharmacia and Becton Dickinson, each for a 6-month period. Statistical analyses to assess quality control parameters for the various methods revealed that the T4 assay had greater precision and reproducibility than either of the 2 commercially available TSH kits. The number of false negative results was similar for both methods. Eight infants with ectopic thyroid glands were correctly detected by the T4 method. One infant with secondary hypothyroidism was detected by the T4 approach and missed by the TSH methodology. Three infants overall would have been missed using either the T4 or TSH approach. These data indicate that primary T4 screening has similar sensitivity compared to TSH kits for mass screening programs for congenital hypothyroidism.