Little or no data are available on the immunotoxicity of the new deoxycytidine analogue, gemcitabine (2'-2'-Difluorodeoxycytidine, dFdC). The drug was tested on natural killer (NK), interleukin 2-activated killer (LAK) and antigen-dependent cytotoxic effector cells (CTL) activity. NK cells were treated for 16 hours and then tested against K562 cell line. LAK cells were pretreated for 16 hours before or after IL2 stimulation, and tested against DAUDI cells on day 4. CTL were pretreated for 16 hours on day-1 or on day 4 of coculture, and then tested against MT-2 on day 5. Cytotoxic activity was evaluated by a 4 hours 51Cr-release assay. The results indicate that dFdC inhibits markedly LAK or CTL generation, but does so less efficiently on "mature" LAK or CTL lymphocyte function and only slightly on NK cell activity. Therefore dFdC can be considered immunotoxic for either natural or antigen-dependent cell-mediated immunity.