In a randomized clinical trial, the effects of standard doses of alpha-interferon (alpha-IFN) compared with the effects of half of these doses were evaluated in patients with hairy cell leukemia. There were 14 patients treated with standard-dose (3 MU/day i.m. for 6 months, then 3 MU three times/week for a further 6 months) and 10 patients with low-dose alpha-IFN (1.5 MU/day with the same schedule and for the same period). The overall response rate, the quality, and the duration of response were rather similar in both groups. The rapidity of response in normalizing the peripheral blood counts was similar, even increased in low-dose-treated patients, consisting mainly in clearing the number of circulating hairy cells (p less than 0.03). Finally, the toxic effects of both regimens were minimal but less evident in patients treated with low-dose alpha-IFN. Despite the small number of patients, on the basis of this report, we can confirm that 1.5 MU/day of alpha-IFN is an adequate treatment for patients with hairy cell leukemia.