Alveolar macrophages were isolated from lung lavage fluids taken from BCG-vaccinated and nonvaccinated guinea pigs 2 and 4 wk after challenge with virulent Mycobacterium tuberculosis H37Rv by the respiratory route. Animals had been maintained on either purified, protein-adequate (30%) or protein-deficient (10%) isocaloric diets for 6 wk prior to respiratory challenge. Protein deficiency was accompanied by loss of dermal tuberculin reactivity, even in animals with extensive tuberculosis. Vaccination with BCG failed to protect guinea pigs on the low protein diet. Based on phagocytosis of heterologous erythrocytes with time in vitro, the percentage of actively phagocytic alveolar macrophages remained relatively constant, but the rate of erythrocyte uptake was significantly depressed as the disease progressed, especially in nonvaccinated guinea pigs. However, neither measure of alveolar phagocyte activity was affected by dietary treatment. Protein deficiency does not appear to alter the initial host-parasite interaction in the lungs of tuberculosis guinea pigs but exerts a deleterious effect on anamnestic responses, including tuberculin reactivity and antimycobacterial resistance, in BCG-vaccinated animals.