A large molecular weight sodium dodecyl sulfate (SDS)-insoluble polymer was isolated from rat liver and shown to be a product of transglutaminase activity by virtue of its high epsilon(gamma glutamyl)lysine content. Antiserum raised against this polymer crossreacted with another product of transglutaminase activity, the apoptotic envelope isolated from cultured hamster fibrosarcoma cells. The amino acid composition of isolated apoptotic envelopes and the SDS-insoluble polymer were found to be comparable, although not identical. Using the polymer antiserum, the apoptotic index (mg polymer protein per mg DNA) of normal and tumor tissue was determined and found to correlate with the associated transglutaminase activity. Localization of proteins involved in polymer formation in neonatal rat liver cells was found immunohistochemically to be in those cells undergoing apoptosis; these cells also stained selectively for transglutaminase. Several proteins from liver homogenate were found to crossreact with the antipolymer serum, notably proteins of 120, 80, 43 and 38 kDa.