Model systems of respiratory infection in mice were established with Streptococcus pneumoniae, influenza virus, and Mycoplasma pulmonis. The LT50 for S. pneumoniae was 2 1/2 days, for lethal influenza 6 days, and for M. pulmonis 5 days. Morbidity in sublethal influenza infections reached a peak during days 5 to 10, with recovery indicated by the third week. The course of each pulmonary infection was followed by use of the animal's maximal ability to consume oxygen (VO2max by determining the weight, compliance, and stability of the excised lung, and in some cases by following O2 consumption of minced tissue. Depression of VO2max began early in each infection; reductions ranged from 9% at the peak of sublethal influenza infection to 50% 12 to 48 hr before the LT50 of fatal infections. The depressions were not relieved by 100% O2. The noninvasive VO2max test, evoked by cold air, was simple, rapid, and reproducible and appeared to serve as a quantitative measure of over-all function during infection. Each type of infection caused an increase in lung weight, with the largest noted during fatal Mycoplasma illness and lethal influenza. The effects on lungs by influenza and M. pulmonis infections were similar but could be differentiated from those with S. pneumoniae. With sublethal influenza, CL was reduced 30% between days 5 to 10, with recovery by the third week. Ctis was not affected. M. pulmonis infections and lethal influenza caused depressions in CL of over 60% by day 4 but only a 30% decrease in Ctis. The data suggest that the decreased compliance in influenza and M. pulmonis infections was due primarily to increased surface tension. In contrast, S. pneumoniae did not affect compliance.