Safranin O was added to the fixation process in an attempt to retain the soluble proteoglycans and to increase the electron density of these polyanions. Following fixation in the presence of this cationic dye, proteoglycan localization was visualized by light microscopy. In marked contrast, the incubation studies using the proteoglycan digesting enzyme papain revealed a colorless matrix as no Safranin O staining occurred. The ultrastructural findings were consistent with the light microscope observations. Proteoglycan intensity was greatest about the metabolically active chondrocytes and almost totally absent about the degenerative cells. The papain-digested samples exhibited a matrix solely occupied by collagen.