We have developed and validated a method for imaging inflammation using a monoclonal antibody (1.2B6) against E-selectin, an endothelial-cell specific adhesion molecule. This study was undertaken to compare 111In-1.2B6 with 99Tcm-labelled non-specific IgG (99Tcm-HIG) in the detection of synovitis in 11 patients with rheumatoid arthritis (RA). Imaging was performed 4 h and 20-24 h post-injection (pi) of 555 MBq 99Tcm-HIG and 15 MBq 111In-1.2B6. Scintigraphic results were compared with clinical scores of joint involvement. Joint uptake was semiquantitated. The scintigraphic appearances with both tracers correlated well, although 111In-1.2B6 at 24 h showed the highest detection rate. Taking joint tenderness or swelling as evidence of clinical activity, the sensitivity of 111In-1.2B6 at 4 h and 24 h was 69% and 82%, respectively, compared with 69% and 62% for 99Tcm-HIG. 111In-1.2B6 also displayed abnormal activity over a number of joints that appeared silent on clinical examination. Joint-to-soft tissue ratios were higher for 111In-1.2B6 at 24 h (4.0 +/- 1.9; p < 0.0001 vs all) than at 4 h (2.4 +/- 1.4) or than for 99Tcm-HIG at 4 h and 24 h (1.6 +/- 0.5 and 2.3 +/- 0.7, respectively). Net 111In counts over joints increased significantly between 4 h and 24 h (mean change: 54 +/- 40%). This study demonstrates that 111In-1.2B6 scintigraphy is a sensitive method by which to assess RA activity and that targeting is more intense and specific than using 99Tcm-HIG. However, the optimum time for 111In-1.2B6 scintigraphy is 24 h whereas good results are already obtained with 99Tc-HIG at 4 h pi. Current efforts are directed at developing 99Tcm-labelled 1.2B6 for imaging endothelial activation.