Specific pathogen-free guinea pigs were infected via the respiratory route with viable, attenuated Mycobacterium tuberculosis H37Ra and maintained on purified isocaloric diets. The control diet contained 30% protein (ovalbumin) and 50 ppm of added zinc (50 micrograms/g), the low protein diet contained 10% protein and 50 ppm of added zinc, and the low zinc diet contained 30% protein and no added zinc. Guinea pigs from each diet treatment were skin tested with purified protein derivative 48 h before sacrifice at 3, 4, and 5 weeks postinfection. Protein-deficient animals exhibited significantly reduced body weight, spleen weight, serum total proteins, and serum albumin. Zinc deficiency was characterized by loss of weight and progressive reductions in plasma zinc concentrations. The number of viable M. tuberculosis H37Ra cells was significantly higher in the lungs of both malnourished groups at 3 weeks, but fell below control viable counts by 5 weeks postinfection. A similar pattern was seen in the spleens and bronchotracheal lymph nodes. Both the proportion and intensity of delayed hypersensitivity reactions increased steadily between 3 and 5 weeks in control animals, whereas the two malnourished groups were essentially anergic at all intervals, despite systemic infection. These results demonstrate that both protein and zinc deficiencies exert a significant influence on the development of pulmonary tuberculosis but that the nature of the influence depends upon the interval studied. In both malnourished groups, the pulmonary infection tended to peak early and decline, whereas the disease developed more slowly in control animals. Apparent control of mycobacterial populations in the tissues was accomplished by malnourished animals in the absence of demonstrable delayed hypersensitivity.