In December 1987, the Italian Cooperative Study Group for Hairy Cell Leukemia (ICGHCL) started a multicenter trial designed with the aim of investigating the possible role of splenectomy in HCL patients responding to initial treatment with a-IFN. Patients aged less than 65 years, diagnosed within 6 months, were included into the trial and treated with a-IFN (3 MU/daily) for 3 additional months after the achievement of CR or for a maximum of 12 months, regardless of the quality of the response. Patients in CR could undergo splenectomy while patients achieving PR after 12 months of treatment were randomized between splenectomy and maintenance therapy. By June, 1992, the trial closed, with 182 enrolled patients. Nine were subsequently determined to be not eligible while nine additional patients were lost at follow up. One hundred and sixty-nine patients were assessable for both response and survival. At the end of the induction therapy with a-IFN (mean time of treatment 16.9 months), 29 CR (17.7%), 100 PR (61.0%), 26 minor responses (MR) (15.8%) and 9 (5.5%) treatment failures occurred. At the last follow up (March, 1993), with a mean follow up of 39 months, 5 patients had died and the overall survival rate at 4 years was 96%. Twelve patients underwent splenectomy after CR. After a mean follow up of 8.6 months, 8 relapses occurred. Thirty-one out of 100 were randomized between splenectomy (16 cases) and maintenance therapy (15 cases). The low accrual was mostly due to the rejection of randomization by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)