The amino-terminal domain of fibronectin has a fibrin binding site and a site for covalent cross-linking to fibrin. This fibrin binding domain was isolated from human recombinant fibronectin and labeled with In-111; the final molecular weight was 12 kD. It was applied to a pilot study of 62 patients; 30 who were thought to have deep vein thrombosis and 32 controls. All 30 patients had either impedance plethysmography, duplex ultrasound, contrast venography, or various combinations of the three. Eight disagreements in the 30 patients suspected of having deep vein thrombosis were registered between fibrin binding domain imaging and the other examinations. Three of the patients with negative scan results had clots that were 1 week old or older, and this may be a limitation of the technique. In three other patients who had negative scan results, but positive alternative studies, there was a history of previous episodes of deep vein thrombosis and this could be a cause of false-positive results in the other modalities. There was one documented false-negative scan in a fresh clot. Normal scans were obtained in the lower extremities of the control patients, except in two who demonstrated uptake at the sites of insulin injections. The initial results of this feasibility study are encouraging and warrant further investigation.