Interleukin 12 (IL12, NKSF-natural killer stimulatory factor) was found to stimulate natural killer (NK) cell activity of hairy cell leukemia (HCL) patients. Two patients not responding to IL12 stimulation were also resistant to interferon alpha (IFN alpha)-mediated augmentation of NK activity. IL12 also enhanced slightly the interleukin 2 (IL2)-induced cytotoxicity of HCL patients, while IFN alpha reduced the stimulatory effect of IL2. These data suggest that interleukin 12 has NK modulatory properties in HCL leukemia patients, which may be different from those of IFN alpha.