Objective. Reasons for apparent primary deposition of calcium pyrophosphate dihydrate (CPPD) crystals in some synovial membranes have not been systematically examined. We undertook the present study to investigate for and compare possible cellular and matrix factors related to the presence of these crystals in synovium and cartilage.Methods. Ten synovial membrane specimens and 6 cartilage specimens were obtained at the time of joint surgery from 10 patients with CPPD crystal deposition disease, for light microscopic (LM) and electron microscopic (EM) studies.Results. In all synovial and cartilage specimens, we found many of the small CPPD crystals aligned on or in parallel to collagen fibers, as seen by EM. In 9 of the Submitted for publication September 9, 1992; accepted in revised form December 1. 1992. 10 crystal-containing synovia, we found foci of chondrometaplasia adjacent to CPPD, by LM. In 7 of the synovia, including the one without LM evidence of chondrometaplasia, we observed the presence of chondrocytelike cells by EM. We did not note any predictable relationship between the crystals and matrix vesicles, either in synovium or in cartilage.Conclusion. Our EM findings provide evidence of the relationship of small CPPD-like crystals, presumably early forms, to collagen fibers both in synovium and in cartilage. By LM and EM, we also demonstrate evidence of a close association between chondrometaplasia and CPPD deposits in synovium. We suggest that chondrometaplasia might be responsible for synovial CPPD formation in predisposed patients. Both the collagen fibers and chondrocyte-like cells seem to be involved in the primary formation of CPPD deposits in the synovium as well as in the cartilage.In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, crystals appear to deposit virtually only in articular and periarticular connective tissues, mainly fibrocartilage, hyaline cartilage, and synovium, and, less often, in tendons, ligaments, and bursae (1-3). The proposed mechanisms involved in CPPD deposition in cartilage include increased production or impaired removal of calcium and inorganic pyrophosphate (PPJ (1,2,4-6), decreased magnesium concentrations (7,8), and various cellular and matrix factors, which can promote, nucleate, or inhibit crystal deposition (1,2,9).Local tissue factors probably play an important role in CPPD deposition disease and possibly determine the preferential articular localization of crystal deposits. McCarty et a1 described CPPD deposits