In vitro treatment of thymocytes and splenocytes with rabbit complement (C') alone induced significant reductions in the proportion of NK-T cells in murine system. The reduction appeared to be prominent in the thymic NK-T cells compared to that in splenic NK-T cells. No reductions were detected in other populations, such as T, B and NK cells. Thus, NK-T cells lineage-specifically showed the enhanced C' sensitivity. However, NK-T cells in T cell receptor (TCR) transgenic mice of RAG-/- background that lack B cells and antibodies exhibited no C' sensitivity. On the other hand those from the same TCR transgenic mice of RAG intact background that have a normal population of B cells and antibodies showed the C' sensitivity similar to that in normal mice. These findings suggest that the enhanced C' sensitivity observed in the NK-T cell population is associated with the NK-T specific autoantibodies. Indeed, we found that a subset of NK-T cells in the thymus bound mouse immunoglobulins. Similar observations were obtained with several strains of lupus model mice, some of which show a decrease of NK-T cells with aging. Possible roles of the enhanced C' sensitivity of NK-T cells in pathophysiological conditions in various mouse strains including lupus models are discussed.