We investigated the use of bisphosphonates, analogs of pyrophosphate that bind to mineralized tissue, to image renal calculi in vivo. Twenty stone-bearing kidneys in 15 patients without urinary obstruction were studied. 99mTechnetium-methylene diphosphonate was injected intravenously followed by 20 mg of furosemide 4 hours later, and images were obtained by gamma counter for 30 minutes. Areas of increased uptake corresponded with the sites of calculi, and even small or radiolucent calculi were easily seen. Counts in the region of each kidney, the L4 vertebral body, and a background area were combined to calculate a scintigram index (SI) for each kidney. The mean SI of the stone-bearing kidneys was 4.8 +/- 3.5 v 1.3 +/- 0.4 for the normal kidneys. There was correlation of the SI with stone composition and size but not with radiographic density. After correction for size, the SI of stone-bearing kidneys remained significantly higher than the SI of normal kidneys, but the differences between calculi of different compositions were diminished. Nonetheless, high SI values were associated with soft types of calculi and low values with hard types. Future investigations will reveal if this association is constant and if there is any relation between bisphosphonate uptake and response to lithotripsy. The sensitivity of urolithoscintigraphy to image small or radiolucent calculi may make it an effective technique for the assessment of residual fragments after lithotripsy.