Synovial fluid (SF) was obtained from 40 patients with varying grades of osteoarthritis (OA) of the knee and examined by transmission electron microscopy to ascertain how frequently hydroxyapatite crystals (HA) were present and whether they were related to disease severity or putative markers or promoters of cartilage resorption. HA crystals were conspicuous and abundant in specimens from 21 of the 40 patients studied. Patients in whom HA was present had significantly larger effusions (13.0 +/- 8.9 vs 8.7 +/- 6.1 ml, p less than 0.05). They also tended to have radiologically more severe disease (radiological grade: 2.91 +/- 0.92 vs 2.39 +/- 0.85, p = 0.056). No difference in keratan sulfate (KS) concentrations was observed. Moreover, despite the presence in some specimens of numerous free histiocytes which were actively phagocytosing HA aggregates, the concentrations of interleukin 1 beta (IL-1 beta), a monocyte product with cartilage and bone resorbing activity, were below the limit of detection (20 pg/ml). Our results confirm that HA crystals are a common finding in patients with OA of the knee and show that HA is associated with larger effusions, but not increased SF concentrations of cartilage proteoglycan substituents (KS) or IL-1 beta.