Vitamin E supplementation has been shown to contribute in immunoregulation, antibody production, and resistance to implanted tumors. Similarly beta-carotene has been shown to down-regulate growth factors which contribute towards proliferation of pre-malignant cells. We embarked upon a study to evaluate the effect of vitamin E and beta-carotene on natural killer (NK) cells, which perform tumor surveillance role in the mammalian body. Mouse splenocytes or human peripheral blood lymphocytes were used as NK cells with murine YAC-1 lymphoma or human K-562 lymphoma cells, respectively, as target cells. The NK cells were treated with vitamin E or beta-carotene while target cells were labeled with sodium 51chromate. Both cell types were then reacted for 4 hours. The NK cell tumorolytic activity was measured by the chromium release assay. Oral administration of alpha-tocopherol at a dose of 100 mg/d in mice showed a significant increase in NK cell activity. Similarly, treatment of NK cells with alpha-tocopherol in vitro at doses 0.5 mg/ml, 1-0 mg/ml, and 2.0 mg/ml increased the tumorolytic activity of NK cells. Tocotrienol showed a similar response at ten times lower dose. When NK cells were treated with varying concentrations of palm vitee (mixture of alpha-tocopherol and tocotrienol), maximum effect was observed at the dose mixture of 12 micrograms and 24 micrograms alpha-tocopherol and tocotrienol, respectively. When murine NK cells were treated in vitro with beta-carotene at doses ranging from 2 ng/mg to 200 ng/ml, a decrease in tumorolytic effect was observed. However, human NK cells after treatment with beta-carotene at doses ranging from 0.1 microgram/ml to 10 micrograms/ml showed a significant increase in tumorolytic function. NK cells were also obtained from mice that had been parenterally administered beta-carotene and alpha-tocopherol. These experiments showed no significant increase in the NK cell function.