OBJECTIVE To determine the presence of circulating autoantibodies to desmoglein (Dsg) 1 and Dsg 3 in patients with oral lichen planus. METHODS Serum concentrations of circulating autoantibodies to Dsg 1 and Dsg 3 were determined by ELISA in 32 patients with erosive form and 25 patients with reticular form of oral lichen planus, 13 patients with acute recurrent aphthous ulcerations and 50 healthy controls. Indirect immunofluorescence analysis was also performed. RESULTS Concentrations of circulating autoantibodies to both Dsg 1 and Dsg 3 detected in the sera of patients with erosive form of oral lichen planus were significantly increased in comparison with those in healthy controls, patients with recurrent aphthous ulceration, and those with reticular oral lichen planus (P<0.001 for both anti-Dsg autoantibodies). Indirect immunofluorescence also revealed significantly more positive findings in patients with erosive oral lichen planus (18 positive of 22 tested) than in healthy controls (1 positive of 20 tested; P<0.001), patients with recurrent aphthous ulceration (1 positive of 10 tested; P<0.001), and those with reticular oral lichen planus (3 positive of 15 tested; P<0.001). CONCLUSIONS Humoral autoimmunity seems to be involved in the pathogenesis of oral lichen planus. The differences in the serum concentration of desmoglein autoantibodies suggested that pathological mechanisms in erosive and reticular forms of oral lichen planus might not be the same.