The aim of our study was to evaluate the occurrence of chondrocytes containing alpha-smooth muscle actin in human normal and diseased cartilage. Immunohistochemistry using monoclonal antibodies for alpha-smooth actin, muscle-specific actin, S-100 protein, CD 34, and desmin was performed on samples of human articular cartilage obtained at autopsy following sudden death, during total hip and knee replacement for osteoarthritis, or after femoral neck fracture in patients without symptoms of osteoarthritis. Moreover, the layers of residual cartilage from chondral posttraumatic defects obtained during preoperative arthroscopy and of newly formed cartilage after autologous-chondrocyte transplantation (Hyalograft C) obtained during second-look arthroscopy were also examined by immunohistochemistry and RT PCR. Our study showed that a significant percentage of articular chondrocytes express alpha-smooth muscle actin in healthy, diseased, and regenerated articular cartilage. Alpha-actin positive chondrocytes (18%) were observed predominantly in the upper zone of normal articular cartilage. By contrast, only approximately 10% of cartilage cells in the deep region stained for this contractile actin isoform. Actin-positive chondrocytes (myochondrocytes) are formed predominantly in response to injury to the osteoarthrotic cartilage, at sites of defective healing, and in newly formed cartilage after autologous chondrocyte transplantation. Fibrocartilage is present in some of these conditions, and it is known that this tissue contains chondrocytes with actin. The presence of myochondrocytes in the surface layer of normal articular cartilage indicates that this region probably plays an important role in maintaining cartilage integrity. Myochondrocytes may utilize the contractile actin isoform in manipulating the extracellular matrix of articular cartilage. It is also possible that actin-containing chondrocytes have a higher potential for regeneration in contrast to chondrocytes that do not contain this contractile material in their cytoplasm.