Some patients in apparent complete remission of hairy cell leukemia (HCL) after 2-chlorodeoxyadenosine (2-CdA) treatment may have minimal residual disease (MRD). This study examines detection of minimal residual disease by immunohistological staining using the monoclonal antibody (MoAb) B-ly 7 in 11 patients with complete remission of hairy cell leukemia (HCL) after 2-CdA therapy administered between 1990 and 1993. In all 11 cases, residual hairy cells could be detected by MoAb B-ly 7 (0.1 to 7.5%, median 0.65%). At a follow-up period of 7 - 29 months (median 19.3), 9 of these patients remained in complete remission, whereas 2 patients relapsed 22 and 27 months after 2-CdA therapy. To determine whether flow-cytometric analysis of hairy-cells in bone marrow aspirates and peripheral blood cells are comparable with results obtained by immunostaining with B-ly 7 in bone marrow biopsies, available data using CD-19/CD-11c double-staining were analyzed. In 5 of 10 cases no hairy-cells could be detected in bone marrow aspirates, and in 6 partly different cases no hairy-cells were detectable in peripheral blood using flow-cytometry, although immunostaining of bone marrow biopsies using B-ly 7 revealed hairy-cells (ranging form 0.1 to 7.5%) in these cases. These results indicate that therapy with 2-CdA does not eradicate hairy cell leukemia despite complete remission according to conventional criteria. Minimal residual disease might be responsible for subsequent relapse. We conclude that routine immunohistological examination of bone marrow biopsies with B-ly 7 should be performed for assessment of MRD. Flow cytometric investigations of mononuclear cells of bone marrow aspirate or peripheral blood seem valuable for regular long term monitoring of MRD, but does not substitute for immunostaining of bone marrow biopsies.