We have previously identified statin, a nonproliferating-cell-specific nuclear protein of 57,000 dalton whose presence can be used to distinguish between growing and nongrowing cells. In this report we identify another protein, terminin, whose presence (by immunofluorescence microscopy) can be used to distinguish between temporarily and permanently growth-arrested cells. Thus terminin is a marker to separate the senescent from the quiescent state. By means of an unique monoclonal antibody (mAb1.2), the presence of terminin is recognized as granules in the cytoplasm of in vitro aged fibroblasts; these granules are not found in serum-starved, contact-inhibited, growing or transformed fibroblasts, except for those cells experiencing the initiation of apoptosis due to long-term deprivation of nutrients. Preliminary histochemical studies show that terminin is also found in the superficial epithelial layer of the esophagus, where terminal differentiation is followed by apoptosis and sloughing off into the lumen. Biochemical characterization by Western blot shows the terminin antibody recognizing a protein of 84 kilodalton (kDa) in growing and quiescent cells, whereas in senescent cells a protein of 57 kDa is recognized; this result suggests that a senescence-dependent protease may cleave the 84 kDa protein to 57 kDa. This proteolytic action seems to render the specific antigenic epitope exposed in its native state and accessible to the terminin antibody by immunofluorescence microscopy. It is this product of posttranslational modification in the form of a cytoplasmic 57 kDa protein that is the marker distinguishing between senescence and quiescence.