Fifty-three hairy cell leukemia patients were treated with low dose recombinant and natural alpha-interferon for 7 or 13 months with a marked improvement in peripheral blood and bone marrow findings. Our results suggest that daily injections have no advantage over three weekly injections, but longer treatment (12-13 months) is better than shorter treatment (6-7 months). The possibility of a relapse raises the issue of the place of splenectomy in the treatment strategy. Since the definition of remission and of relapse is based on the histological changes in the bone marrow, the necessity for the quantification of the hairy cell infiltration on bone marrow sections is stressed.