The role of in vivo administration of lymphoblastoid alpha-interferon (IFN-alpha) on the immune status of 12 patients with hairy cell leukemia (HCL) was studied. In most cases an increase in T3(CD3), T4(CD4), and T8(CD8) lymphocyte subsets was documented at the same time as hairy cells disappeared from the circulation. This led in most cases to an improved T4/T8 ratio. The effect of treatment with IFN-alpha was particularly evident on the natural killer cell compartment, which is often functionally depressed in HCL at diagnosis. After therapy, a progressive increase in the cytotoxic activity was observed in most patients. This was more evident 6-9 months after commencing treatment. These findings suggest that, in addition to the known clinicohematological effects, IFN-alpha can improve both the T and natural killer compartments in patients with HCL.