SAG12, an Arabidopsis gene encoding a cysteine protease, is expressed only in senescent tissues. Studies of the expression patterns of a variety of genes showing senescence-specific or senescence-preferential expression indicate that plant senescence involves multiple regulatory pathways. In this study it is shown that the expression of SAG12 is specifically activated by developmentally controlled senescence pathways but not by stress- or hormone-controlled pathways. Using SAG12 as a molecular marker for the study of developmental senescence, we show that cytokinin, auxin, and sugars can repress developmental senescence at the molecular level. Studies using promoter deletions and recombination of promoter fragments indicate that a highly conserved region of the SAG12 promoter is responsible for senescence-specific regulation, while at least two other regions of the SAG12 promoter are important for full promoter activity. Extracts from young and senescent Arabidopsis leaves contain factors that exhibit differential binding to the senescence-responsive promoter element.