The gene encoding manganese superoxide dismutase (MnSOD) from Drosophila melanogaster has been isolated and its expression has been studied. In contrast to several mammalian MnSOD genes, the Drosophila gene contains a single intron and is transcribed into a single 0.8-kb transcript. Whole-mount in situ hybridization reveals extensive transcript accumulation in ovarian nurse cells and a heavy maternal contribution to the early embryo, Larval imaginal discs are enriched with MnSOD transcripts relative to other larval tissues, further suggesting a possible relationship between high MnSOD expression and mitotic activity. The 5'-upstream region contains several well-known regulatory elements including metal response, antioxidant response, and xenobiotic response elements (MRE, ARE, and XRE, respectively), sites for activator protein-1 (AP-1), nuclear factor-kappa B (NF-kappa B), adenosine 3',5'-cyclic monophosphate regulator binding element factor (CREB), as well as classic TATA and CAAT boxes. That MnSOD expression in Drosophila is regulated in part by the transcription factor AP-1 via the MAP kinase signal transduction pathway is suggested by experiments which show that a hypomorphic mutation of the MAP kinase-encoding rolled gene substantially reduces levels of MnSOD transcripts and correlates with reduced resistance to oxidative stress in rolled mutants.