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Background: Very rapid bone loss, osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions. Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented, or at least attenuated, by pamidronate and other bisphosphonates., Method: We prospectively studied 26 male patients undergoing renal transplantation, and randomized them to receive either placebo or intravenous pamidronate (0.5 mg/kg) at the time of transplantation and again one month later. All patients received immunosuppression comprising prednisolone, cyclosporine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry (DXA)., Results: Twelve months after transplantation, the mean (+/- SEM) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4% (P < 0.05). In contrast, patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae. At the femoral neck, placebo-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas there was no significant change in the pamidronate treated group. The two study groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the serum creatinine and PTH concentration were found in the two groups. Apart from transient hypocalcemia in two patients, no significant adverse effects of pamidronate were noted., Conclusion: This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later. The regimen was simple to administer, well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients.