The latent form of transforming growth factor-β (TGF-β) in human milk and platelets was converted to the active form when conscious, pylorus-ligated mice were given human milk and platelets by intragastric intubation. Oral administration of TGF-β exerted enhancing effects on the natural killer (NK)-cell activities in spleen and liver. Augmentation of NK-cell activities in spleen was observed for 7 days after oral administration of TGF-β. TGF-β at concentrations of 5 and 20 ng produced the greatest augmentation of NK-cell activities in spleen. However, NK-cell activities in spleen were unaffected when TGF-β was given intravenously. Interleukin (IL)-12 production in spleen was enhanced by oral administration of TGF-β, but not by intravenous administration of TGF-β. These findings suggest that large amounts of TGF-β in human milk are involved in early antiviral protection through the augmentation of NK-cell activities.