Patients with malabsorption syndromes have an increased risk of kidney stone formation. Those with cystic fibrosis (CF) suffer from extreme forms of steatorrhea, but they are not reported to be prone to kidney stone formation. Risk parameters for renal stone formation were studied in the urine of 43 patients with cystic fibrosis and compared to those of 5 patients with calcium oxalate nephrolithiasis and 21 healthy controls. Patients with CF showed increased urinary concentrations of oxalate, phosphate, xanthine and uric acid, and decreased concentrations of magnesium and citrate, comparable to concentrations found in patients with calcium oxalate stones. However, compared to stone bearing controls the calcium concentration was markedly decreased in the urine of CF patients. Our results suggest that hypocalciuria in CF seems to protect against nephrolithiasis despite the presence of lithogenic factors. Calcium supplementation instituted for clinical reasons may result in an increased risk for kidney stone formation. This risk may be diminished by additional administration of magnesium as well as allopurinol.