AN IMMUNOLOGICAL comparison of ODU Plaque-Resistant (RES) and Plaque-Susceptible (SUS) Rats was performed in order to determine if plaque accumulation was secondary to some immunological abnormality, and to ascertain the effects of plaque accumulation on the immune system. Plaque accumulation in SUS rats on powder diets is associated with a significant elevation in immunoglobulin levels over RES rats, especially in serum IgG and IgM. Young (less than 9 weeks) SUS rats possess fewer splenic T lymphocytes than do young RES rats. This decrease is associated with a marked decrease in the response of spleen cells in vitro to T cell mitogens, Con A and PHA. This decrease is unrelated to diet and is completely and spontaneously reversed in the adult (3 month) rats. These studies demonstrate that the accumulation of large amounts of plaque cause an elevation in immunoglobulin levels. However, plaque accumulation in SUS rats does not appear to be secondary to any demonstrable immunologic abnormality.