Inflamed joints in human rheumatoid arthritis (RA) can be imaged employing 99Tcm-labelled anti-CD4 monoclonal antibodies (MAbs). These MAbs recognize the CD4 molecule expressed on T-helper cells and, with a lower density, on macrophages, which are both abundantly present in RA inflammatory infiltrates. However, it is at present unclear whether specific binding to target molecules in the inflamed joint determines the joint uptake of anti-CD4 MAbs, i.e. whether the uptake of anti-CD4 MAbs differs from that of control immunoglobulins with irrelevant specificity. Eight patients with severe, active RA were examined after intravenous injection of a 99Tcm-labelled murine anti-human CD4 MAb (MAX.16H5; 200-300 micrograms, 370-550 MBq) or polyclonal human immunoglobulin (HIG; Technescan, MDH-67, Mallinckrodt Diagnostica; 1 mg, 370 MBq); five patients received both the anti-CD4 MAb and HIG. Whole body and joint scans in anterior and posterior views were obtained 1, 4 and 24 h after injection. As early as 4 h after injection, the anti-human CD4 MAb showed a higher target-to-background ratio in arthritic knee and elbow joints in comparison to polyclonal HIG used for conventional imaging, indicating that that anti-CD4 MAb allows more specific detection of inflammatory infiltrates rich in CD4-positive cells.