Circulating immune complexes were isolated by 2% polyethylene glycol precipitation from the sera of 15 out of 37 patients with Behçet's syndrome and 11 out of 23 patients with recurrent oral ulcers. The antigenic cross-reactions of the polyethylene glycol precipitates were studied by coating a plastic tube with one complex and adding another 125I-labeled complex in dissociating (acid) conditions. On neutralization, partial reassembly occurred with the complex coating the tube wall, thus indicating cross-reaction with it. In the first 30 complexes studied, the cross-reactions obtained were sorted by computer program into two mutually exclusive subsets of reactions. Two similar homologous subsets of reactions were found in the second group of 29 patients: in total, nine out of 16 ocular, four out of six herpetiform circulating immune complexes in one subset, and four out of seven neurological in the other. A wider pattern of reaction could be detected in addition, which induced most of the Behçet's syndrome and recurrent oral ulcers. Immune complexes from control sera did not cross-react. An exogenous agent could account for the circulating immune complexes' cross-reactions for the group as a whole, and two antigenic determinants of that agent or antigens from different damaged tissues explain the subsets.