Our goal was to determine if HLA DRB1*13 is associated with autoimmune hepatitis in North American patients. Two hundred and ten adults with definite type 1 autoimmune hepatitis were typed by DNA-based techniques, and the frequency of HLA DRB1*13 in patients without DRB1*03 and DRB1*04 was compared to that in 396 patients with eight other chronic liver diseases and 102 normal individuals. HLA DRB1*13 occurred more commonly in the autoimmune patients who lacked DRB1*03 and DRB1*04 than normal subjects who were similarly restricted (56% vs. 27%, P = 0.007). The frequency of HLA DRB1*13 was higher in autoimmune patients without DRB1*03 and DRB1*04 than in patients with other chronic liver diseases who were similarly restricted (59% vs. 32%, P = 0.01). Only patients with primary sclerosing cholangitis had a comparable occurrence of HLA DRB1*13. In conclusion, HLA DRB1*13 may be a genetic risk factor for some white North American patients with type 1 autoimmune hepatitis.