Charcot neuroarthropathy is one of the most devastating complications of diabetes causing much discomfort and disability and sometimes leading to amputation. The current therapies are disappointing and fail to address the underlying disease process. In order to try and halt the underlying bone resorption we have studied the action of the bisphosphonate, pamidronate, in six diabetic patients with active Charcot neuroarthropathy. The treatment was associated with improvement in the patients' symptoms and a reduction in Charcot activity as measured by temperature of the affected foot which fell from 3.4 +/- 0.7 (SE) degrees C to 1.0 +/- 0.5 degrees C above the intact foot (p = 0.05). There was a significant reduction in bone turnover as judged by alkaline phosphatase activity which fell by 25 +/- 3% (p < 0.001). These preliminary data suggest that bisphosphonates may be the first definitive treatment for active Charcot neuroarthropathy and that controlled trials are now indicated.