Renal cortical scintigraphy has been reported to be useful in children for confirmation of the diagnosis of acute pyelonephritis. Subsequent experimental studies have demonstrated that dimercaptosuccinic acid (DMSA) scintigraphy, when compared directly with histopathology, is highly reliable for the detection and localization of parenchymal inflammatory changes associated with acute pyelonephritis. Recent clinical studies of acute pyelonephritis using DMSA scintigraphy reveal that the majority (50 to 91%) of children with febrile urinary tract infections have abnormal DMSA renal scan findings and that the majority of these children do not have demonstrable vesicoureteral reflux. However, when vesicoureteral reflux is present, renal cortical abnormalities are demonstrated by DMSA scintigraphy in 79 to 86% of the kidneys. In children with febrile urinary tract infections routine clinical and laboratory parameters are not reliable in the differentiation of acute pyelonephritis, documented by DMSA renal scan findings, from urinary tract infections without parenchymal involvement. Furthermore, the presence of P-fimbriated Escherichia coli associated with febrile urinary tract infections does not reliably predict those kidneys that have acute parenchymal inflammation demonstrated by DMSA renal scans. DMSA is also the isotope agent of choice for the detection of renal scarring. Clinical studies report greater sensitivity of DMSA renal scintigraphy for the detection of renal scarring when compared with the excretory urogram, particularly in infants and young children. In a recent prospective study of post-pyelonephritic renal scarring in children we found that acquired renal scarring only occurs in sites corresponding exactly to previous areas of acute pyelonephritis demonstrated by DMSA scintigraphy at the time of infection. Furthermore, once acute pyelonephritis occurs, ultimate renal scarring is independent of the presence or absence of vesicoureteral reflux. These findings provide convincing evidence that renal parenchymal infection, rather than vesicoureteral reflux, is the prerequisite for acquired (postnatal) renal scarring. Vesicoureteral reflux as a risk factor for acquired renal scarring is directly related to its role as a risk factor for acute pyelonephritis. We conclude that DMSA scintigraphy is a valid tool for confirming the diagnosis of acute pyelonephritis in children and for identifying kidneys at risk for subsequent renal scarring.