The potential of whole urine of stone-formers and normal controls to precipitate crystals of calcium oxalate dihydrate from ions endogenous in urine was investigated by the method of rapid evaporation to 1250 mOsm/kg and subsequent freezing. Over 90% incidence in crystallization was achieved in the two groups. When the population density and size of these crystals were compared, it was found that 50% of urine samples from stone formers (30-50 years of age) were rich in crystal-nucleating and growth-inhibiting factors and the other 50% were not different from normal controls. These effects were observed when polyanionic macromolecules recovered from pooled urine samples of stone-formers or normal controls were dissolved in urine ultrafiltrate and similarly tested. That the urinary polyanions were the active modifiers in the test system was further corroborated by the reversal of crystallization activity of urine samples and the urinary polyanions after they had been through an acidification-reneutralization procedure. The urinary polyanionic macromolecules were found, after enzymatic and/or chemical treatment, to contain chondroitin sulphates, dermatan sulphates, heparan sulphates and glycoproteins.