Eleven previously untreated patients with B-chronic lymphocytic leukemia (B-CLL) (eight in Binet's stage A, two in stage B and one in stage C) received therapy with alpha-2a interferon (Roferon AR, Hoffman, La Roche) at a rather low dose (3.0 MU) given intramuscularly three times a week for a total of 14 weeks. In all cases an objective, although transient, response as measured by a decrease in the absolute lymphocyte count was observed (P less than 0.05). In four patients an increase in the absolute number of granulocytes in the peripheral blood could be detected. Characteristically the response was obtained early after starting treatment (median 4 weeks). None of the patients achieved a complete remission. Interestingly, a stage C patients with thrombocytopenia not due to hypersplenism and a non-diffuse pattern of bone marrow disease obtained significant improvement in the platelet count. Interferon was well tolerated by most patients without major toxicity. These results suggest that alpha-interferon may be useful in the therapy of previously untreated B-CLL patients with a low tumor burden.