In this study we present new differential characteristics of NK cells expressing CD56 surface antigen in low (CD56 dim ) or high (CD56 bright ) density. In contrast to CD56 bright NK cells CD56 dim cells express killer cell immunoglobulin (Ig)-like receptors (KIR) such as CD158a, CD158b, and NKB1. However, c-type lectin-like receptors (KLR) CD94/NKG2 and CD161 are present on both subsets. The ability to form conjugates with susceptible targets is approximately twice as strongly pronounced in CD56 dim vs. CD56 bright NK cells. Last but not least, granules of CD56 dim cells contain about tenfold more perforin and granzyme A enabling potentially more effective cytolysis compared to CD56 bright NK cells. On the other hand, CD56 bright NK cells are superior in producing the proinflammatory cytokines IFN-+ (28.5% vs. 20.8%, p X 0.05) and TNF- § (28% vs. 15.8%, p X 0.001). The different NK cell populations retained their specific phenotype in vitro during culture in the presence of IL-2 contradicting that they simply display different stages of maturity. Taken together our data support the view that CD56 bright cells are specialized NK cells that regulate immunological response mechanisms rather by cytokine supply than by their cytotoxic potential. The poor cytolytic capacity of CD56 bright NK cells can be explained by weak ability in forming conjugates with target cells and low contents of perforin and granzyme A in their granules.