Five Drosophila melanogaster genes belong to the highly conserved sir2 family, which encodes NAD(+)-dependent protein deacetylases. Of these five, dsir2(+) (CG5216) is most similar to the Saccharomyces cerevisiae SIR2 gene, which has profound effects on chromatin structure and life span. Four independent Drosophila strains were found with P-element insertions near the dsir2 transcriptional start site as well as extraneous linked recessive lethal mutations. Imprecise excision of one of these P elements (PlacW07223) from a chromosome freed of extraneous lethal mutations produced dsir2(17), a null intragenic deletion allele that generates no DSIR2 protein. Contrary to expectations from the report by Rosenberg and Parkhurst on their P-mobilization allele dSir2(ex10), homozygosity for dsir2(17) had no apparent deleterious effects on viability, developmental rate, or sex ratio, and it fully complemented sir2(ex10). Moreover, through a genetic test, we ruled out the reported effect of dSir2(ex10) on Sex-lethal expression. We did observe a modest, strictly recessive suppression of white(m4) position-effect variegation and a shortening of life span in dsir2 homozygous mutants, suggesting that dsir2 has some functions in common with yeast SIR2.