The authors describe a 16-year-old girl who has suffered from chronic natural killer cell lymphocytosis (CNKL) for 12 years. From age 4 years, she has shown a persistent lymphadenopathy and lymphocytosis. Clinically, she developed allergic skin involvement, thrombocytopenia, and peripheral polyneuropathy. Annual flow cytometry analyses of lymphocyte subsets revealed persistently elevated NK cell levels (55-75% of the lymphocyte fraction and 0.7-10 x 10(3) NK cells per microliter of blood). Furthermore, IgE serum concentrations were markedly increased. Based on CD16, CD161, and CD94 surface antigen expression, the NK cell population was characterized as mature NK cells. Functional analysis of these cells showed a 2-fold increase of intrinsic cytotoxic activity toward K-562 cells compared with NK cells from healthy controls. The authors present a clinical case of rare CNKL. The patient's NK cells possess significantly increased cytotoxic activity. These findings are discussed in context with elevated IgE concentrations.