The evaluation of the rare patient who presents with oral and genital aphthae or almost constant, multiple (>3) oral aphthae, but no systemic signs or symptoms (i.e., complex aphthosis), is difficult because no laboratory test is available to exclude Behçet's syndrome. Six patients with complex aphthosis were evaluated. In addition, patients with simple aphthosis, those with seronegative arthritis, and normal controls were assessed for circulating immune complexes (CIC) by in vitro and in vivo assays and for neutrophil migration by subagarose methods, since these tests have given significant results in patients with Behçet's syndrome. Patient 1, with complex aphthosis, had Raji cell evidence for CIC (51.2 mg aggregated human gamma globulin Eq/ml), Clq, and C3 in dermal blood vessels 4 hours post intradermal histamine injection and had a Sweet's syndrome-like vasculitis 24 hours post histamine injection. In addition, her serum enhanced the migration of patient neutrophils (3.6 ± 0.6 to 4.6 ± 0.5; N = 6, p ≤ 0.01). All other test and control patients had negative or normal CIC and neutrophil migration determinations. Sixteen-month clinical follow-up has confirmed that Patient 1, but not Patients 2 to 6, has developed overt manifestations of Behçet's syndrome.