Studies were conducted in young guinea pigs to determine the effects of malnutrition on selected variables of host resistance. Malnutrition was produced differently in two experiments. In the first the quantity of a standard, normal diet was reduced progressively so that test groups were fed 25% less each week over a 4 week period. Control groups were fed ad libitum. In the subsequent experiment, animals were fed defined guinea pig diets containing 5%, 30%, and 60% casein, respectively, which were similar in caloric content, vitamins, and minerals. Measurements of phagocytic bactericidal activity, serum opsonization, serum IgG and C3 levels, and mitogenic response of lymphocytes were made at weekly intervals. Results obtained from both experiments were comparable. There was a significant decline in phagocyte function by the third week in malnourished animals while the numbers of phagocytes per milliliter of peritoneal washings were similar to controls at all time periods. A depression of serum opsonization was observed when animals became moribund even though serum IgG levels remained unchanged. Serum C3 levels in malnourished animals were significantly lower than controls. Mitogenic response of lymphocytes to phytohemagglutinin was 85% lower in the 5% casein group after the third week. These results indicated that a marasmus-like condition and protein malnutrition depress critical functions of resistance.