Although sonography is useful in the evaluation of renal transplants, there are no objective sonographic findings for reliably differentiating acute rejection from cyclosporine nephrotoxicity. This study was undertaken to determine the role of pulsed Doppler flow analysis (duplex sonography) in making this distinction. Duplex Doppler sonography was performed in 106 patients with normally functioning transplanted kidneys and in 34 patients with renal transplant dysfunction who underwent percutaneous biopsy. Renal vascular impedance was estimated in the segmental, interlobar, and arcuate arteries by calculating the ratio of end-diastolic minimum velocity to systolic peak velocity (diastolic/systolic ratio). In the healthy control subject, the diastolic/systolic velocity ratios varied in the different arterial segments, ranging from a mean of 0.23 in the segmental arteries to a mean of 0.32 in the arcuate arteries. Seventeen patients experienced acute rejection: eight of the nine with acute vascular rejection had abnormal Doppler ratios; eight patients with acute cellular rejection had normal ratios. Nine patients with cyclosporine nephrotoxicity all had normal duplex scans. Seven patients with chronic rejection had normal ratios. One patient with hemolytic-uremic syndrome had an abnormal flow pattern. These findings indicate that duplex sonography may be useful in differentiating acute vascular rejection from cyclosporine nephrotoxicity in the transplanted kidney.