In vivo, articular chondrocytes produce an important amount of extracellular matrix (cartilage) whose quality is impaired upon inflammation or aging leading to arthritis or arthrosis. Transglutaminases (EC 2.3.2.13) are a family of enzymes which have been shown to be involved in extracellular matrix stabilization, cell differentiation and possibly in initiation and propagation of inflammatory diseases. It is therefore of interest to study transglutaminase activity in chondrocytes. Transglutaminase activity was studied in rabbit articular chondrocytes in primary culture, where cells are in a well-differentiated state as assessed by collagen-type synthesis, as well as in subculture and in retinoic acid-treated cells, where cells are in a dedifferentiated state. Results showed that two different TGases activities are expressed in chondrocytes. One, down-regulated upon retinoic acid treatment of cells, preferentially membrane bound and strongly activated upon trypsin treatment of cell lysates, is expressed at a high level in primary culture. The other one is up-regulated upon retinoic acid treatment, preferentially cytosolic and inactivated upon trypsin treatment of cell lysates. The rate of expression of the TGase down-regulated by RA seems to correlate with the differentiation state of the chondrocyte. This suggests that this TGase activity may have a physiological role in cartilage and merits further study.