Alpha-2b interferon (alpha-2b IFN), administered at 2 x 10(6) U/m2 three times per week is highly effective in the treatment of progressive hairy cell leukemia (HCL) and in the retreatment of patients who have relapsed after previous IFN therapy. To determine if a lower interferon dose would induce a comparable antileukemic effect with less toxicity, a-2b IFN was administered at 2 x 10(5) U/m2 subcutaneously three times per week to 17 patients with progressive HCL. Thirteen patients had HCL in relapse after a previous response to alpha-2b IFN; four patients were previously untreated. The median duration of treatment was 9 months. Toxicity consisted only of transient, mild flu-like symptoms in two patients. Of the 13 previously IFN-treated patients, four had a minimal response, one had no response, and eight had progressive disease. Of four previously untreated patients, one had a partial response, two had a minimal response, and one had no response. In seven of eight patients whose disease progressed on low-dose IFN, the dose was escalated to 2 x 10(6) U/m2 three times per week, and all seven patients demonstrated hematologic response within 3 months to the dose escalation. We conclude that alpha-2b IFN at 2 x 10(5) U/m2 three times per week is relatively ineffective for the treatment of relapse after previous IFN therapy.