Serial bone-marrow biopsies were obtained from 46 hairy cell leukaemia (HCL) patients at different time intervals during the course of their disease. The patients were treated according to the following schemes: 14 received alpha-lymphoblastoid interferon (alpha-IFN), 11 2-Chlorodeoxyadenosine (2CdA), and 21 alpha-IFN first, followed by 2CdA. All the biopsies were studied by immunohistochemical means for the detection of minimal residual disease. The administration of 2CdA produced the highest reduction of both the tumor burden and HC index, with residual hairy cells (HCs) being undetectable at conventional light microscopy in most cases. In addition, 2CdA induced a higher degree of hypocellularity than alpha-IFN: the reduction in the amount of normal bone-marrow, however, was less pronounced in patients who had alpha-IFN before 2CdA. Of 9 patients who received both alpha-IFN and 2CdA and were followed for more than 2 years, 3 relapsed, while the remaining 6 continued to show rare HCs 2 years after 2CdA administration.