In 10 HCL patients, who following treatment for more than 1 year with alpha-IFN, had achieved a normalization of the splenomegaly and a disappearance of circulating hairy cells together with a complete restoration of all peripheral hematological values, a multiple assessment of the apparent complete remission (CR) was carried out. The presence of residual disease was investigated by bone marrow histology, bone marrow immunohistochemistry, immunoglobulin (Ig) gene analysis and on the basis of the serum levels of the soluble form of the Interleukin-2 receptor (sIL-2R). Examination of bone marrow biopsies showed a pattern of CR in 5 cases; 4 of them revealed no evidence of Ig heavy chain gene rearrangement, as well as a near normalization of the serum levels of sIL-2R. Immunohistochemical studies were carried out on embedded paraffin sections with the monoclonal antibody 4KB5 (CD45R) and were assessable in 4 of the 5 patients considered in CR and in 3 of the 4 cases with no Ig gene rearrangement. In 2 the pattern of CR was confirmed, while in the 3rd a minimal but persistent disease (5%) was suspected.