Using monoclonal antibodies to surface antigens, we typed and quantitated the mononuclear cells (MNCs) infiltrating liver tissues from 23 patients with primary sclerosing cholangitis. The circulating T lymphocytes were also enumerated by flow cytometry in 12 of these patients. In blood, T lymphocytes and especially T8+ cells were decreased. T cells were the major components of MNCs (78%) in portal tracts. Few of these cells were Tac+ or HLA-DR+. Total MNCs (929 +/- 90 vs. 106 +/- 18 in controls) included 11% M1+ and 8% B1+ cells. Aggregates of T4+ and T8+ cells were common in portal areas. The portal T4/T8 ratio of 1.27 +/- 0.1 was significantly (p less than 0.01) different than that around proliferating bile ductules (0.8 +/- 0.1). The T8+ and M5+ cells localized in these areas of proliferation and infiltrated ductal epithelium. On the other hand, T4+ cells accumulated on the parenchymal side of fibrosed tissue and densely surrounded certain intralobular bile ducts. Even late in the disease, variability in the extent of MNCs infiltration, ductal proliferation and periductal fibrosis was seen in each biopsy.