We have previously demonstrated that DNA can be extracted from the dried blood specimen of the type used for newborn screening. The technique presented here allows us to extract RNA from newborn screening specimens for cDNA synthesis by reverse transcriptase and amplification by the polymerase chain reaction (PCR). Products of the PCR reaction are then analyzed by restriction enzymes. This method successfully distinguishes beta A and beta S transcripts in unaffected (AA), carrier (AS), and affected (SS) individuals. The value of this approach for identification of a compound heterozygous patient with S/beta-thalassemia, using the original newborn screening specimen, is also demonstrated. This work shows that mRNA is stable in dried blood specimens and that analysis of the mRNA phenotype can be a useful adjunct in the application of molecular genetic technology to newborn screening.