Cholelithiasis has been reported to occur rarely in infants. To determine the incidence of cholelithiasis in infants receiving furosemide, we prospectively performed ultrasonograms on 86 patients. We studied 42 patients receiving furosemide (subjects) and 44 patients not receiving furosemide (controls). There was a significantly higher incidence of gallstones in subjects (21%) than in controls (2%) (P less than .05). When followed over 1 year, the gallstones did not resolve. There were no significant differences in the dosage of furosemide, gestational age, placement of umbilical venous catheters, or amount of total parenteral nutrition (TPN) between subjects with and without gallstones. However, subjects received more days of TPN (16.7 +/- 15.1) than controls (8.4 +/- 13.2) (P less than .05). These data show that the incidence of cholelithiasis is higher than previously suspected in infants receiving furosemide. Thus, furosemide, either independently or in conjunction with the use of TPN, predisposes infants to the development of cholelithiasis.