To determine the significance of antinuclear antibodies and their patterns of indirect immunofluorescence in type 1 autoimmune hepatitis, sera from 99 patients were evaluated. Patients with antinuclear antibodies had a lower frequency of liver transplantation (6% vs 22%, P = 0.04) than seronegative patients. They were also more commonly HLA-DR4-positive than seronegative patients (56% vs 30%, P = 0.05) and normal subjects (56% vs 30%, P = 0.004). The 42 patients with antinuclear antibodies and a diffuse pattern of indirect immunofluorescence had higher serum titers of ANA (serum titers > or = 1:500, 71% vs 14%, P < 0.0001) and SMA (serum titers > or = 1:500, 69% vs 27%, P = 0.003) than the 22 patients with antinuclear antibodies and a speckled pattern. These patients, however, were otherwise not distinguished by clinical features and treatment response. Patients with a speckled pattern had A1-B8-DR3 more frequently than patients with a diffuse pattern (65% vs 23%, P = 0.005) and normal subjects (65% vs 13%, P < 0.0001), but they had no other salient features. We conclude that patients with antinuclear antibodies have a better long-term prognosis than seronegative patients, and they have HLA-DR4 more commonly. The patterns of indirect immunofluorescence associated with ANA positivity have no practical clinical implications.