The effect of dietary protein restriction in mice on the capacity of their lymphoid cells to induce graft-vs.-host responses (GVHR) was studied. Mice were fed diets containing 4% or 20% protein ad libitum. The GVHR capacity of cells from all lymphoid organs of deprived mice was increased on a cell-for-cell basis over that of their normally fed counterparts. The slope of the dose-response curves did not change for spleen and mesenteric lymph node cells although their reactivity was increased by fourfold, and 50% respectively. The slope of the curves for thymus and Peyer's patches was changed indicating fundamental changes in the reactive cellular populations of these organs. Changes in GVH reactivity of cell populations from deprived mice were not mediated by increased corticosteroid production as adrenalectomy did not reduce their GVH responses. An explanation for the results was sought in a general decrease in production of short-lived cells with a rapid turnover such as most B cells. Long-lived T cells appear to persist and retain their reactivity for quite long periods in the face of nutritional insults.