We have isolated chromosomal deoxyribonucleic acid clones containing the Drosophila dopa decarboxylase gene. We describe an isolation procedure which can be applied to other nonabundantly expressed Drosophila genes. The dopa decarboxylase gene lies within or very near polytene chromosome band 37C1-2. The gene is interrupted by at least one intron, and the primary mode of regulation is pretranslational. At least two additional sequences hybridized by in vivo ribonucleic acid-derived probes are found within a 35-kilobase region surrounding the gene. The developmental profile of ribonucleic acid transcribed from one of these regions differs from that of the dopa decarboxylase transcript.The dopa decarboxylase (DDC) gene of Drosophila melanogaster is of considerable interest for a study of gene regulation. It is a well-characterized genetic locus, and it displays a complex pattern of developmental expression which is hormonally regulated during at least part of the life cycle. We have initiated a study of the structure and expression of this gene using recombinant deoxyribonucleic acid (DNA) techniques.DDC is an essential enzyme in the pathway of sclerotinization, the process of cuticle tanning and hardening in Drosophila. It is localized primarily in the hypoderm. DDC activity is developmentally regulated, showing major peaks at the time of puparium formation and again at adult eclosion (22, 26). The first major peak of enzyme activity parallels a rise in titer of the molting hormone , B-ecdysone (16, 20), and the available evidence suggests that 8i-ecdysone is required for the appearance of this enzymatic activity (20,25). In contrast, the second major peak of activity, at adult eclosion, is not correlated with an elevated f8-ecdysone titer. This activity, which occurs some 90 h after pupariation, occurs when ,B-ecdysone levels are very low and have been low for some 40 h (16). Thus, the two major inductions of DDC activity appear to be induced by dissimilar mechanisms.The