Abstract Background/Aims: Human leukocyte antigens DR3 and DR4 influence susceptibility for type 1 autoimmune hepatitis and affect its immunological manifestations. We aimed to determine if autoimmune features in patients with chronic liver diseases other than autoimmune hepatitis are associated with these same antigens. Methods: One hundred and seventy-eight patients were evaluated. Class II typing was performed by restriction fragment length polymorphism in all patients and 80 normal subjects Results: One or more autoantibodies, including antinuclear antibodies (28%), smooth muscle antibodies (8%), thyroid antibodies (18%) and antimitochondrial antibodies (13%), were found in 92 patients (52%). Concurrent clinical diseases of an immunological nature were recognized in 53 patients (30%). Patients with antinuclear antibodies had a higher frequency of the A1-B8-DR3 haplotype than patients without these antibodies (27% versus 12%, p=0.04) and patients with concurrent immunological diseases had a higher frequency of HLA DR4 than patients without this antigen (51% versus 26%, p=0.003). Patients with antinuclear antibodies were more commonly DR3 positive than normals (35% versus 16%, p=0.03) and patients with concurrent immunological diseases were more commonly, HLA DR4 positive than normals (51% versus 30%, p=0.02). Conclusions: We conclude that the clinical expression of antinuclear antibodies is associated with the A1-B8-DR3 haplotype and the presence of concurrent immunological diseases is related to the DR4 antigen. These clinical manifestations have a genetic basis that is not disease-specific.