Urine contains inhibitors of calcium oxalate (CaOx) crystal growth. One such inhibitor is nephrocalcin (NC), a glycoprotein which is made in the kidney and contains several residues of gamma-carboxyglutamic acid (Gla) per molecule. The presence of Gla may be important to its ability to inhibit crystal growth. Several studies suggest that vitamin K-dependent proteins may also play a role in renal calcium (Ca) handling, and that vitamin D deficiency may lead to excess urinary Ca loss, but the effect of the vitamin K antagonist warfarin on urinary Ca excretion and CaOx growth inhibition in humans is not known. We studied 11 men while they were taking warfarin for a mean of 252 days, and again a mean of 64 days after its discontinuation. Urinary Ca excretion did not differ between those on or off warfarin, or between those on warfarin and normal controls. The ability of the subjects' urine to inhibit CaOx crystal growth did not differ on or off warfarin, or from that of control urine, and the excretion of immunoreactive NC also did not differ between these groups. NC was found to be responsible for approximately 16% of the CaOx growth inhibition seen. These results do not suggest that vitamin K-dependent proteins play a major role in renal Ca excretion in men, or that interference with vitamin K alters NC excretion or inhibitory activity of the urine.