We studied the proliferative mechanism of granular lymphocytes (GL) in patients with granular lymphocyte proliferative disorders (GLPD) including granular lymphocyte leukemia (GLL). Both T- and natural killer (NK)-lineage GLPD cells expressed only the IL-2 receptor beta chain (p70-75) on their surface and had proliferative responses to IL-2. Incubation of T-lineage GLPD cells with immobilized monoclonal antibody (MoAb) OKT3 (anti-CD3), and NK-lineage GLPD cells with immobilized MoAb 3G8 (anti-CD16) induced IL-2 production and cell proliferation, and the cell proliferation was inhibited by anti-IL-2 MoAb and anti-IL-2 receptor MoAb. These results suggest that GLPD cell proliferation is mediated, at least in part, through an IL-2-dependent autocrine pathway.