Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of 99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of 99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. The phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion, 99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.