To test the effect of dietary protein restriction on mitogenesis and the mixed leukocyte reaction in the mouse immune system, 2 protocols were followed: a 4% protein diet ad lib and a standard diet of 24% protein fed only on alternate days, Monday, Wednesday and Friday (intermittent feeding). The effect of dietary restriction was tested on weanling animals, placed on the dietary regimes for 1 and 6 mo. periods and adult animals (17 mo. of age) for 6 mo. of restriction. Dietary restriction had a profoundly suppressive effect on mitogenesis and MLC [mixed leukocyte culture] during the 1st mo. of growth (i.e., weanling animals tested after 1 mo. restriction). After 6 mo. of continued restriction suppression was no longer observed in the weanling animals. The 17 mo. old animals placed on restricted dietary regimes for 6 mo. showed results similar to the control group. The intermittently fed animals presented a more complex picture. Initial suppression of the responses, observed in weanling animals after 1 mo. of restriction gave way to responses significantly higher than control levels after 6 mo. of dietary restriction. The results were discussed in terms of a general model of immunological stress.