The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells.In vitro81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6.In vivothe plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6–3.8% injected dose/g in 2–6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumountissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for131I-81C6 Fab than131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2fragments are required.