HLA-A, B, Cw, DR and DQ antigens were serologically determined in 105 patients suffering from lichen planus (LP). Of these patients, 87 had idiopathic LP and 18 had secondary LP. In the first group, 43 had cutaneous LP without mucosal lesions, 17 had cutaneous LP with mucosal lesions and 27 had purely mucosal LP. No HLA antigen was found to be significantly associated with secondary LP or with mucosal idiopathic LP. In cutaneous idiopathic LP with or without mucosal lesions, the HLA-DR1 and DQ1 antigen frequency was significantly increased, and that of HLA-DQ3 significantly decreased. Among the HLA-DR1 cutaneous idiopathic LP patients, 78.5% carried the DRB1*0101 allele, and 21.4% the DRB1*0102 allele, compared with 35.7 and 67.8%, respectively, of the HLA-DR1 controls. Our data demonstrate that idiopathic LP is influenced by HLA-associated genetic susceptibility and resistance factors not involved in secondary LP, and that cutaneous idiopathic LP is a genetically and therefore pathogenetically different condition from purely mucosal idiopathic LP.