For a study of the ultrastructural pathology of chondromalacia patellae, we studied biopsy specimens that had been obtained at operation in twelve young patients who had pain in the anterior aspect of the knee due to mechanical derangement and also had the pathological changes in articular cartilage that are characteristic of chondromalacia. The initial pathological finding was swelling of the superficial matrix associated with breakdown of the collagen fiber network, especially at matrix streaks in the superficial and transitional zones. Fibrillated cartilage contained surface fissures that penetrated the middle layers. Amorphous electron-dense material was found covering the internal surfaces of the fissures; this appeared to contain degraded components of the matrix. In association with these changes, there were formation of nests of cells (clusters of chondrocytes) and increased numbers of organelles in the chondrocytes. A limited repair reaction also was observed in some specimens; this was characterized by the migration of fibroblast-like cells over the surface of the cartilage. The ultrastructural observations on these specimens from patients who had chondromalacia were compatible with a pathogenesis resulting from mechanical overload.