Fifty infants weighing less than 1200 grams at birth who survived at least 3 weeks were enrolled in this study, of whom 14 (28%) developed sonographic evidence of nephrocalcinosis by 9 weeks, despite median total furosemide dose of only 2 mg/kg. Risk factors for development of neonatal nephrocalcinosis were white race (P < 0.01) and positive family history of kidney stones (P < 0.001). Sonography demonstrated echogenic foci measuring 2 to 9 mm near the papillary tips in most infants with nephrocalcinosis even though the kidneys apparently had not progressed through the stages of diffuse medullary echogenicity that Patriquin and Robitaille postulated are the sonographic correlates of the Anderson-Carr-Randall progression, a leading theory of renal calculus formation. The presence of intratubular calcifications in the two patients studied post mortem also is contrary to the Anderson-Carr-Randall theories that center on interstitial calcium deposition. Although neonatal nephrocalcinosis shares some clinical risk factors (white race and positive family history of renal calculi) with renal calcium deposition in older children and adults, the prevalent theories of renal calcium deposition do not account for its sonographic or histologic manifestations.