High dietary intakes (100-2500 mg/kg diet) of vitamin E (dl-alpha-tocopheryl acetate) modified the functions of splenic lymphocytes and alveolar macrophages (AM). The numbers of splenocytes and AM obtained from male F344 rats fed high vitamin E diets significantly increased at 10 d after the onset of the experiment. Splenic lymphocytes' responses to concanavalin A and natural killer cell activity also increased with increasing contents of vitamin E in the diets. Furthermore, the ability of AM to phagocytose opsonized sheep red blood cells increased with increasing contents of vitamin E in diets and showed a fivefold increase in rats fed the diet with the highest vitamin E content (2500 mg/kg diet) compared with rats in the control group. The lavage fluid of lungs from rats fed a high vitamin E diet (500 mg/kg diet) increased phagocytic activity of AM from rats fed a basal diet; it also induced a 72% increase in activity compared to that in control rats. The phagocytic activity of AM was not enhanced when the large molecules (MW greater than 10,000) were removed by ultrafiltration from the lavage fluid of lungs of rats fed the high vitamin E diet (500 mg/kg diet). These data suggest that there is macrophage-activating factor-like material in the lavage fluid of lungs of rats fed high vitamin E diets and that high vitamin E diets may activate not only splenic lymphocytes but also AM.