The transcription of manganese superoxide dismutase (MnSOD), expression of which is essential for detoxification of superoxide radicals from mitochondria, has been shown to be regulated in vitro by many factors and conditions including oxidative stress, cytokines, lipopolysaccharide, cytoplasmic myc (c-myc), p53 and tumour necrosis factors. Here we describe genomic regions in Drosophila melanogaster with regulatory effects on transcription of the MnSOD gene at an organism-wide level. To understand the integrated regulation of MnSOD expression we screened chromosomes of D. melanogaster to locate deficiencies that altered the expression of MnSOD. Suppressors of MnSOD were screened by assessing the relative message abundance of MnSOD in 149 deletions covering approximately 81% of the Drosophila genome. The chromosomal deficiency Df(2R)017 significantly up-regulated MnSOD mRNA by 1.7-fold. Deficiency in four other genomic intervals, Df(1)ct-J4, Df(2L)BSC4, Df(3L)66C-G28 and Df(3R)Scr, down-regulated MnSOD expression. Changes in MnSOD expression were positively associated with paraquat sensitivity of the deletion genotypes. Thus, at least one candidate enhancer and four candidate suppressors exist in the Drosophila genome to regulate the transcriptional activity of the MnSOD gene in vivo.