The lesion-to-nonlesion 24 hour/4 hour ratio of technetium-99m methylene diphosphonate (MDP) uptake was used to distinguish osteomyelitis from increased bone uptake caused by adjacent soft-tissue infection. In a prospective study, this ratio was measured in 38 patients with 41 sites of increased uptake that were suspected to be osteomyelitis. The mean ratio was 1.18 +/- 0.18 in patients with proved osteomyelitis, which was significantly higher (P less than .001) than that in patients with increased uptake resulting from soft-tissue infection (0.98 +/- 0.05). On the basis of a receiver operating characteristic curve, a ratio of 1.06 was selected as the cutoff for differentiating osteomyelitis from soft-tissue infection. This method resulted in a sensitivity of 82%, a specificity of 92%, and an accuracy of 85%, and it appears to be more reliable than three- and four-phase scintigraphy, which are subjective and nonquantitative techniques.