Factors influencing the nucleation of monosodium urate (NaHU) were studied with supersaturated solutions of sodium urate at physiologic conditions of temperature, pH, and ionic strength. Spontaneous nucleation of NaHU did not occur at urate concentrations of 5 mM (84 mg%) in the presence of 140 mM Na ion. Addition of synovial fluids from gout patients greatly enhanced nucleation, whereas fluids from degenerative joint disease patients moderately enhanced nucleation, and fluids from rheumatoid arthritis patients had only a slight effect. Hyaluronic acid and purines minimally enhanced urate crystallization, whereas other connective tissue components had no effect.