Interest in the assessment of activity of Paget's disease has increased since the advent of effective therapies. The aim of this study was to develop a quantitative method for the scintigraphic assessment of Paget's disease activity in bone. Twenty patients with Paget's disease were studied prospectively. A scintigraphic visual activity index, together with a quantitative activity index that reflects both the extent and activity of the disease, was obtained for each patient. The quantitative activity index is calculated as the sum of the activity (geometric mean measured from the anterior and posterior views) for all affected bones divided by a reference obtained in non-affected bone. To evaluate the validity of the scintigraphic methods, several biochemical markers of bone turnover were assessed: serum total alkaline phosphatase and serum propeptide aminoterminal of type I procollagen (PINP) as markers of bone formation; urinary hydroxyproline and urinary N-terminal cross-linked telopeptide of type I collagen (NTx) as markers of bone resorption. The visual and quantitative scintigraphic indices were highly correlated (r = 0.78, P < 0.0001). The highest correlations between the biochemical markers and the quantitative activity index were found for PINP (r = 0.69, P < 0.001), which was the most sensitive marker of bone formation, and for urinary NTx (r = 0.63, P < 0.005), which was the most sensitive marker of bone resorption. In conclusion, quantitative evaluation of bone scintigraphy allows easy and objective assessment of Paget's disease activity and it may be useful in evaluating the effectiveness of therapies.