Hyperuricosuria appears to cause calcium oxalate nephrolithiasis by promoting the formation of monosodium urate or uric acid crystals, which either act as seed crystals for calcium oxalate or adsorb normally occurring macromolecular inhibitors of calcium oxalate crystallization. Both mechanisms require that hyperuricosuria cause excessive supersaturation of the urine, but this has not yet been studied under conditions of normal lifestyle. We have measured the saturation with respect to sodium hydrogen urate and the concentration of undissociated uric acid in the urine samples of 67 patients with calcium nephrolithiasis, who had idiopathic hypercalciuria, hyperuricosuria, both, or neither disorder. Patients with hyperuricosuria excreted urine that was supersaturated with respect to monosodium urate or undissociated uric acid more frequently than did other stone formers or normal subjects, and are therefore at a greater risk of forming a solid phase of monosodium urate or uric acid. Treatment measures that lowered uric acid excretion also lowered urine saturation, and this may be the reason that such treatment tends to prevent calcium stone recurrence.