Two long-term cell lines obtained from two cases of large granular lymphocyte lymphocytosis (LGLL) displaying an unusual phenotype are reported here. Patient n. 1 was CD2+ CD3- CD16+ CD8+ CD56- CD57- CD29+ CD45RA+, whereas patient n. 2 was CD2-CD3+ CD8+ CD16+ CD56- CD57+ CD29+ CD45RA+. The cells were large granular lymphocytes by light and electron microscopic criteria and displayed strong antibody-dependent cell mediated cytotoxicity (ADCC) and NK activity. Northern blot analysis revealed aberrant transcripts of TCR beta chains for patient n. 1, and full length TCR alpha and beta transcripts for patient n. 2. In both cases, we were able to establish a long term cell line which functionally revealed strong ADCC and NK activity. Functional implications of these 2 subpopulations are discussed.