The incidence of renal stone disease in patients receiving topiramate (Topamax) is 2-4 times that expected in the background population. This has been attributed to a weak carbonic anhydrase inhibitor effect, but published data are scant. Following three cases of renal stones in patients receiving topiramate, we evaluated biochemical risk for nephrolithiasis in eight further unselected patients. Most patients demonstrated inadequate urinary acidification and hypocitraturia; in some cases citrate was undetectable. Several patients also had other risk factors for nephrolithiasis, including increased urinary sodium, calcium and oxalate excretion. The biochemical changes induced by topiramate appear highly penetrant. Experience with this drug is relatively short-lived and it is being prescribed for long-term use in (often) relatively young patients. This report highlights the significantly increased metabolic risk of stone formation in patients receiving topiramate.