The effects of starvation on the cellular immune response of C58/Wm mice to syngeneic malignant lymphoid cells (1_b cells) were studied. Mice were starved 1-3 days before or after immunization. The capacity of starved animals to survive immunization was used to quantify immunosuppression. When starvation bracketed immunization by -1 to + 1 days, only 2 of 23 mice survived primary immunization, compared with 100% survival for nonstarved controls. A 2-day period of starvation + 1 to + 7 days after primary immunization reduced survival about 30%. For a test of the effect of starvation on the secondary immune response, mice were immunized, starved 2 days, and then challenged with viable 1_b cells. When mice were starved from -3 to + 1 days before or after challenge, there was a 25-45% decrease in survival. Starvation caused a disproportionate depletion of lymphoid tissue elements. The proportional loss in the weight of the spleen and thymus was essentially twice as great as the loss in total body weight. The peripheral blood leukocyte count was reduced by about 20% when mice were starved 1 day and by approximately 50% when they were starved 2 days. When mice were starved 1-2 days, the differential leukocyte count did not shift and there was no significant change in the number of blood erythrocytes or in the hematocrit. Starvation for 2 days caused a 65-70% reduction in the number of viable mononuclear spleen cells. Starvation for 3 days caused about 90% reduction. Adoptive cell transfer experiments showed that the immunocompetence of individual spleen immunocytes was not reduced by starvation.