The significance of calcium-containing crystals is unknown. Circumstantial evidence suggests that crystals are associated with more severe arthritis. Addition of calcium pyrophosphate dihydrate crystals to a lapine meniscectomy model of osteoarthritis resulted in greater damage to cartilage compared with meniscectomy alone. Elimination of calcium pyrophosphate dihydrate crystals may occur extracellularly by enzymatic degradation. Spermine and spermidine both enhance the degradative activity of alkaline phosphatase on crystals. In familial calcium pyrophosphate dihydrate crystal deposition disease, genetic heterogeneity is likely because one family demonstrated a linkage to chromosome 8q, whereas another did not. Tumoral deposition of calcium pyrophosphate dihydrate crystals may occur in single locations without radiographic chondrocalcinosis in other joints. Hydroxyapatite crystals are found in the ligamenta flava from surgical speci-mens but not as tumoral depositions. Magnesium whitlockite crystals have been found not only in osteoarthritic articular cartilage but also in normal cartilage, suggesting that these crystals may be nonpathologic in at least some cases.