We describe a patient with a CD3- lymphoproliferative disease of granular lymphocytes (LDGL) characterized by proliferation of CD3-CD16+ GL, restricted to the expression of p58/EB6 antigen and lacking the p58/GL183 antigen. Using PCR analysis we demonstrated the presence of EBV DNA in the peripheral blood mononuclear cells and purified CD16+ GL from the patient; a monoclonal episomic configuration of the virus could not be demonstrated with Southern blot analysis. The presence of EBV DNA was also detected by PCR in the serum; this finding was associated with a serological pattern consistent with a previous, already seroconverted, EBV infection. During a 4-year follow-up the lymphocytosis spontaneously disappeared; interestingly, in terms of the p58 antigen expression, we provided evidence of the reconstitution of a normal pattern of circulating NK subsets (i.e. p58/EB6+ p58/GL183-, p58/EB6+ p58/GL183+, p58/EB6- p58/GL183-, p58/EB6-p58/GL183+). At the time of resolution of lymphocytosis, EBV-PCR analysis still demonstrated the persistence of EBV DNA in peripheral blood mononuclear cells, but not in the patient's serum. By indicating that inciting agents (in this case EBV) are involved in inducing the GL proliferation, our data contribute insights into the pathogenetic mechanisms accounting for in vivo GL accumulation in LDGL. It appears that a second, still unknown, event is required to determine the neoplastic transformation.