Transglutaminase may be an important intracellular regulator of protein function through its ability to catalyze the calcium- dependent covalent linkage of primary amines to glutamine residues in peptide linkage with the generation of ammonia. This study provides further evidence that a major alteration in tumor cells is the marked decline in the expression of transglutaminase activity. This may alter its known protein cross-linking activity and favor lack of differentiation and proliferation.