Groups of specific pathogen-free guinea pigs were randomly assigned to purified, isocaloric diets containing either 30%, 20%, or 10% casein, or commercial stock diet. Each animal was vaccinated subcutaneously with viable bacille Calmette-Guerin (BCG). Seven weeks post-vaccination, groups of guinea pigs from each diet treatment were skin tested with purified protein derivative (PPD) and killed. Animals fed the 10% casein diet exhibited significant reductions in body weight, serum albumin, and hemoglobin levels. Significantly greater number of viable BCG were recovered from the inguinal lymph nodes of malnourished (10% casein) animals than from 30% casein or stock control groups. Skin test responses to PPD were completely absent or markedly suppressed in the 20% and 10% casein groups. Lymphocyte blastogenesis following in vitro stimulation of peripheral blood lymphocytes with a polyclonal T cell mitogen was also reduced inthe 10% casein group. Circulating levels of serum IgM and C3 complement were not influenced by nutritional status while levels of IgG were elevated in 10% and 20% casein groups. These results suggest that malnutrition may impair cell-mediated immune responses on which the efficacy of BCG vaccine depends.