The authors describe a patient with large granular lymphocytosis who presented with fever of unknown origin and jaundice. Immunophenotyping showed that most of the large granular lymphocytes (LGLs) were CD3-, CD16-, and NKH-1 (Leu-19)+ lymphocytes. Lymphocytosis of this subset of LGLs has not been reported. Analysis of T-cell receptor gene showed polymorphic T-cell receptor beta-chain (TCR beta) gene configuration. Functional studies showed reduced natural killer cell function. The clinical course was very aggressive and resistant to chemotherapy. These features again raise the controversial issues of the ontogeny and heterogeneity of LGLs and their relationship to natural killer cells and T-cells.