Monosodium urate monohydrate (MSUM) crystals derived from a tophus surgically removed from patients suffering from gout and MSUM prepared from a supersaturated solution of sodium urate were studied and compared with respect to their ability to: (1) stimulate chemiluminescence (CL) production by human polymorphonuclear (PMN) cells, (2) induce hemolysis of the human red blood cells and (3) induce inflammation when injected in the rat paw and knee joint. Human MSUM crystals were considerably more active in stimulating CL production by PMN cells and in inducing synovial inflammation. Both serum and papain pretreatment of human MSUM crystals caused inhibition of their enhancing effect on CL production by PMN cells. Papain pretreatment only reduced their phlogogenic activity. Uncoated and, to a much lesser extent, serum-coated human MSUM crystals induced secretion by mononuclear cells (MNC) of the factor(s) that considerably enhanced CL production by PMN cells. Both tophus-derived and synthetic crystals appeared to be weak hemolytic agents. Serum pretreatment of synthetic MSUM crystals reduced their hemolytic activity. These results suggest that surface coating, destroyed by papain treatment, was probably responsible for cell activation induced by human MSUM crystals.