For the development and validation of a quantitative approach to the analysis of bone scans after total knee arthroplasty, 39 consecutive patients with 40 prostheses (6 males, 33 females; mean age, 70 years) were scheduled for clinical, radiographic, and scintigraphic examination ranging from 9 to 90 months after surgery. Twenty-seven total knee arthroplasties were considered to be asymptomatic and 13 symptomatic according to the clinical and radiographic findings. Significant differences were found for 99mTc-methylene diphosphonate uptake for femur and tibia and between symptomatic and asymptomatic patients. A reference range was determined for radionuclide uptake in the periprosthetic bone of the 27 asymptomatic total knee arthroplasties; this range was then used to identify loose total knee arthroplasties among the 13 symptomatic knees. With a clinical and radiographic followup performed 1 year after scintigraphy as a standard of comparison, a sensitivity of 88% (7/8) and a specificity of 100% (5/5) was demonstrated. These preliminary results suggest the feasibility of a quantitative approach to the scintigraphic evaluation of total knee arthroplasties after the first postsurgical year.