Fifty-four patients with hairy cell leukemia were treated for 7 months with three types of subcutaneously injected interferon: recombinant interferon alfa-2a from Hoffmann-La Roche (3 X 10(6) U daily); recombinant interferon alfa-2b from Schering (2 X 10(6) U/m2, three times per week); and partially purified human leukocyte interferon alpha from the Finnish Red Cross (3 X 10(6) U daily). After 4 months, in 27 patients hairy cells decreased dramatically (P less than 0.01) while platelets (P less than 0.05), monocytes (P less than 0.01), polymorphonuclear leukocytes (P less than 0.01) and hemoglobin (P less than 0.01) increased (in this order) as treatment progressed. Morphometric parameters were used to estimate the relative volume of hairy and myeloid cells present in bone marrow. Biopsies were performed at the beginning of the study and in the second, fourth, and seventh months thereafter. Bone marrow disorders were slower to improve as compared with blood. Six severe cases of hairy cell leukemia were responsive to treatment, but required special monitoring during the first 2 months. All three interferons studied are efficient. Interferon receptors, oncogene (mRNA levels) expression, and the relationship between PDGF and fibrosis in hairy cell leukemia are under investigation.