Orthodontic tooth movement is dependent upon the ability of mechanical forces to induce remodelling activity within the tooth-supporting alveolar bone. In view of the importance of bone resorption in mediating tooth movement, the aim of this study was to establish if alterations in the osteoclast-specific bone marker tartrate-resistant acid phosphatase (TRACP) 5b could be detected in the sera of patients undergoing orthodontic treatment. The sample consisted of 14 subjects (10 girls and 4 boys) aged 10.5-16.5 years (mean 12.6 years) being treated with fixed appliances and a distalizing headgear. Venous blood samples (3 ml) were collected from the cubital vein pre-treatment (T0) and 2, 4, and 6 months into treatment (T1-T3); serum TRACP 5b levels were quantified using a solid-phase immunofixed enzyme activity assay. When the data were pooled and treated cross-sectionally, a significant increase in immunoreactive TRACP 5b was detected at 2 months (T1) indicating increased bone resorptive activity. However, when the serum profiles of individual patients were recorded longitudinally, a very different pattern emerged, not all patients following the same trend. This is not surprising given normal anatomical variation and differences between the patients in age, gender, and mechanotherapy. Designed as a pilot to demonstrate 'proof of principle', this study is the first to show that the TRACP 5b isoform can be detected in the sera of patients undergoing orthodontic treatment. It further suggests that serum bone marker measurements offer a simple and minimally invasive method for correlating the findings of laboratory and animal experimentation with clinical data.