The dopa decarboxylase gene (Ddc) of Drosophila melanogaster is expressed in the hypoderm and the nervous system and promoter elements mediating differential expression in these tissues have been identified (Scholnick et al., 1986). Here we report an additional mode of regulation; the unique primary transcript of the Ddc gene is spliced to form mRNAs in these two tissues which differ by a single internal exon. In vitro mutagenesis and P-element-mediated transformation were employed to manipulate the tissue-specific expression of these RNAs. This approach demonstrated that regulated splicing rather than differential stability causes the tissue-specific expression of these RNAs and allowed the identification of Ddc enzyme isoforms encoded by each mRNA. The Ddc enzyme in the central nervous system differs from the hypodermal Ddc protein by the addition of 33-35 amino acids on the N terminus.