The effect of various components of serum and synovial fluid (SF) on in vitro urate crystal formation was measured. Serum and SF has been shown to promote urate crystal formation. The component(s) responsible for this promotion was found to be a macromolecule, sensitive to heat denaturation. Albumin, alpha and beta globulins and chondroitin sulphate had little effect, whereas gamma globulin markedly promoted crystal formation and insoluble collagen also promoted crystal formation in a dose dependent fashion.