The inhibitory activity of whole urines from 32 healthy subjects and 50 calcium oxalate renal stone formers was assessed in terms of their ability to withstand increasing quantities of oxalate before undergoing spontaneous nucleation of calcium oxalate, and their response to a standard 30-mumol challenge of oxalate above their measured metastable limits. The concentrations of calcium (p less than 0.05), oxalate (p less than 0.05), urate (p less than 0.01) and glycosaminoglycans (p less than 0.005) were significantly lower in the stone formers than in the controls and were associated with a significantly higher 24-h urinary volume (p less than 0.001). The majority of urine samples precipitated envelope crystals of calcium oxalate dihydrate, while the remainder precipitated the monohydrate. A significantly (p less than 0.02) greater proportion of the urines from stone formers than from controls deposited calcium oxalate monohydrate, and this was attributed to a lower concentration of calcium in these urines. The minimum amounts of oxalate necessary to induce crystal nucleation did not differ between the two groups, but when the measured metastable limits were expressed as the product of the total (i.e. endogenous + that added to induce nucleation) concentrations of oxalate and calcium at which precipitation occurred, then these limits were significantly lower (p less than 0.05) in the stone formers than in the healthy subjects. However, when the metastable limits of a subgroup of stone formers and controls matched for 24-h urinary volume and calcium and urate concentrations were compared, no differences between the groups could be discerned.(ABSTRACT TRUNCATED AT 250 WORDS)