This study describes the precise spatial and temporal patterns of protein distribution for aggrecan, fibromodulin, cartilage oligomeric matrix protein (COMP) and cartilage matrix protein (CMP) in the developing mouse limb with particular attention to those cells destined to form articular chondrocytes in comparison to those cells destined to form a mineralized tissue and become replaced by bone. Mouse glenohumeral joints from fetal mice (12-18 days post coitus (dpc) to the young adult (37 days after birth) were immunostained with antibodies specific for these molecules. Aggrecan staining defined the general chondrocytic phenotype, whether articular or transient. Fibromodulin was associated with prechondrocytic mesenchymal cells in the interzone prior to joint cavitation and with the mesenchymal cells of the perichondrium or the periosteum encapsulating the joint elements of the maturing and young adult limb. Staining was most intense around developing articular chondrocytes and much less abundant or absent in those differentiating cells along the anlage. CMP showed an almost reciprocal staining pattern to fibromodulin and was not detected in the matrix surrounding articular chondrocytes. COMP was not detected in the cells at the articular surface prior to cavitation but by 18 dpc, as coordinated movement of the mouse forelimb intensifies, staining for COMP was most intense around the maturing articular chondrocytes. These results show that the cells that differentiate into articular chondrocytes elaborate an extracellular matrix distinct from those cells that are destined to form bone. Fibromodulin may function in the early genesis of articular cartilage and COMP may be associated with elaboration of a weight-bearing chondrocyte matrix.