99Tcm-methylene diphosphonate (MDP) global skeletal uptake (4 h GSU) was determined by quantitative measurement of activity on bone scan images 4 h after injection in whole skeleton regions of interest (ROI) in 16 normal subjects, in five patients with hypertrophic pulmonary osteoarthropathy (HPO) and in 12 with Paget's disease. Values were correlated with those of whole body retention (24 h WBR), and serum bone gla protein (BGP), i.e. osteocalcin, alkaline phosphatase (AP) and type 1 procollagen (P1CP). They were 40% higher in HPO than in the normal controls, while in Paget's disease they increased more in polyostotic than in monostotic patients. A statistically significant difference was noted between 4 h GSU and 24 h WBR values in the two groups of patients compared with the controls. Of the bone metabolism markers, serum AP and P1CP were higher in the patients and positively correlated with their enhanced 4 h GSU values, whereas BGP was always within the normal range. This method may thus be regarded as a useful way of simultaneously determining bone 99Tcm-MDP uptake and altered bone turnover sites, especially in patients with systemic bone disease.