It has been widely demonstrated that natural killer (NK) cells are able to discriminate between normal and abnormal cells on the basis of the interaction of their NKRs with the MHC molecules expressed on the target cells. Recent studies showed that also normal dendritic cells are susceptible to NK cell-mediated lysis. In this work, the potential relationships between the expression of different surface molecules on both immature and mature DC and susceptibility to lysis have been investigated. The reduced density of HLA class I on the surface of immature DC resulted in the only permissive signal to NK cell mediated killing. On the contrary, the remarkable increase in HLA class I molecules detected during DC maturation was strictly related to the resistance to NK cell. Contemporary, no clear evidences of a role for other surface molecules modulated during DC maturation (CD80, CD83, CD86 and CD40), were obtained.