NKR-P1 molecules are involved in natural killing of certain tumour targets. Indeed, the NK1.1 (NKR-P1C) molecule is the most specific serological marker on murine NK cells in C57BL/6 mice. Previous studies of NKR-P1 have indicated that anti-NKR-P1 mAb induced NK cells to kill otherwise insensitive targets, NK cell phosphoinositol turnover and Ca++ flux but it was not previously known if all NK cells were activated. In this study we report that immobilized anti-NK1.1 also specifically induced proliferation as measured by thymidine incorporation. The response required low doses of IL-2 for a synergistic effect. Cells stimulated with anti-NK1.1 + IL-2 displayed characteristic cytolytic activity against a NK-sensitive tumour target, YAC-1. However, anti-NK1.1-stimulated cells displayed delayed proliferation kinetics, heterogeneity of the expression of the very early antigen marker, CD69, and altered expression of the Ly-49 family members when compared to NK cells activated by high concentrations of IL-2. Taken together, these data demonstrate that immobilized anti-NK1.1 triggers only a subpopulation of NK cells.