The somatomedins are a family of low-molecular-weight peptides that are thought to mediate the stimulatory effect of growth hormone on skeletal growth. The cells that are directly responsible for skeletal growth are the chondrocytes of the epiphyseal growth plate, and these are the presumed skeletal target cells for somatomedin. As with other peptide growth factors, the cellular effects of the somatomedins are initiated by the interaction of the growth factor with specific receptors on target-cell surface membranes. Chondrocytes that have been isolated from bovine growth plates were previously found to possess specific surface receptors for the principal growth-hormone-dependent somatomedin, somatomedin-C. These studies indicated that the interaction of growth-plate chondrocytes with somatomedin-C involves specific receptor-binding followed by somatomedin-C internalization by the cell, a process identical to that identified in the mechanism of action of other peptide growth factors in other cells. These studies, however, left unanswered the questions of whether there are differences in binding of somatomedin-C by the different cell populations within the physis and whether somatomedin-C has access to cells in intact tissues. The current studies address these issues and indicate that bovine physeal chondrocytes in situ are accessible to exogenous somatomedin-C, that they specifically bind somatomedin-C in situ, and that cells of different physeal zones bind somatomedin-C differently. Labeled somatomedin-C is specifically bound by cells of all physeal zones. However, the binding is greatest for those cells undergoing active synthesis of DNA in the proliferative zone.(ABSTRACT TRUNCATED AT 250 WORDS)