The gene encoding ribosomal protein S19 (RPS19) has been shown to be mutated in 25% of the patients affected by Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. As the role of RPS19 in erythropoiesis is still to be defined, we performed studies on RPS19 expression during terminal erythroid differentiation. Comparative analysis of the genomic sequences of human and mouse RPS19 genes enabled the identification of 4 conserved sequence elements in the 5' region. Characterization of transcriptional elements allowed the identification of the promoter in the human RPS19 gene and the localization of a strong regulatory element in the third conserved sequence element. By Northern blot and Western blot analyses of murine splenic erythroblasts infected with the anemia-inducing strain Friend virus (FAV cells), RPS19 mRNA and protein expression were shown to decrease during terminal erythroid differentiation. We anticipate that these findings will contribute to further development of our understanding of the contribution of RPS19 to erythropoiesis.