We have used new techniques of cell-length scale quantitative autoradiography to assess matrix synthesis, deposition, and deformation around individual chondrocytes in mechanically compressed cartilage explants. Our objectives were to:​ (1) quantify the effects of static and dynamic compression on the deposition of newly synthesized proteoglycans into cell-associated and further-removed matrices;​ (2) measure cell-length scale matrix strains and morphological changes of the cell and matrix associated with tissue compression;​ and (3) relate microscopic physical stimuli to changes in proteoglycan synthesis as functions of compression level and position within mechanically compressed explants. Results indicate a high degree of structural organization in the extracellular matrix, with the pericellular matrix associated with the most rapid rates of proteoglycan deposition, and greatest sensitivity to mechanical compression. Static compression could stimulate directional deposition of secreted proteoglycans around chondrocytes, superimposed on an inhibition of proteoglycan synthesis;​ these events followed trends for compressive strain in the cell-associated matrix. Conversely, proteoglycan synthesis and pericellular deposition was stimulated by dynamic compression. Results suggest that cell-matrix interactions in the cell-associated matrix may be a particularly important aspect of the chondrocyte response to mechanical compression, possibly involving macromolecular transport limitations and morphological changes associated with fluid flow and local compaction of the matrix around cells.