The spleen cells immune response to sheep red blood cells of C3H/HeJ mice fed a 20 g whey protein/100 g diet is substantially higher than that of mice fed an equivalent casein diet of similar nutritional efficiency. The present study indicates that the observed immunoenhancing effect of the whey protein mixture is dependent on the overall amino acid pattern resulting from the contribution of all its protein components. Whey protein contains substantially more cysteine than casein. Dietary cysteine is considered to be a rate limiting substrate for the synthesis of glutathione which is necessary for lymphocyte proliferation. Our studies show that enhancement of host humoral immune response is associated with greater and more sustained production of splenic glutathione during the antigen driven clonal expansion of the lymphocyte in whey protein fed mice in comparison to mice fed the equivalent casein or the cysteine-enriched casein diet. Hence the efficiency of dietary cysteine in inducing supernormal glutathione levels is greater when it is delivered in the whey protein than as free cysteine. Administration of S-(n-butyl) homocysteine sulfoximine, which reduces splenic glutathione level by half, produces a 4-5 fold drop in the humoral immune response of whey protein diet-fed mice. This is further evidence of the important role of glutathione in the immunoenhancing effect of dietary whey protein.