Recombinant leukocyte A interferon is a highly purified single molecular species of alpha-interferon prepared by recombinant DNA methods. In 1982, a phase II trial to evaluate the efficacy of recombinant leukocyte A interferon for patients with previously treated chronic lymphocytic leukemia was begun, and 19 patients were entered in this study. Patients received one of two dose schedules depending on their pretreatment platelet counts. Those with platelet counts greater than 100,000/mm3 received 50 X 10(6) units/m2 intramuscularly three times weekly, with dose reductions to 25 X 10(6) units/m2 and 5 X 10(6) units/m2 for unacceptable toxicity. Those with platelet counts less than 100,000/mm3 received 5 X 10(6) units/m2 intramuscularly three times weekly. Toxicity was dose-dependent and included fever, chills, fatigue, anorexia, myalgias, headache, leukopenia, and thrombocytopenia. Response was evaluable in all but one of the patients entered in this study. Two of the 12 patients treated with 50 X 10(6) units/m2 had a partial response, three had no response, and seven had progressive disease. Of the six patients starting at 5 X 10(6) units/m2 in whom response was evaluable, two had no response and four had progressive disease. Five patients with progressive disease (three at 50 X 10(6) units/m2 and two at 5 X 10(6) units/m2) had an acceleration of disease while receiving recombinant leukocyte A interferon. It is concluded that the dose and schedule of recombinant leukocyte A interferon therapy tested in this study are not effective in previously treated patients with advanced chronic lymphocytic leukemia.