The immune capacity in the spleen, lung, and pulmonary lymph nodes was studied in adult guinea pigs exposed to concentrations of 5000 and 10,000 ppm of carbon monoxide (CO) for 3 min, 6 or 12 times daily for 3 to 4 weeks. The animals were immunized with sheep red blood cells (SRBC) 7 days before termination of exposure. All except one exposure group showed a lower weight increase than controls. In all but one group a tendency to an increased number of pulmonary alveolar macrophages (PAM) was found and all groups showed a tendency toward an increased number of polymorphonuclear leukocytes (PMN). Reductions in the number of plaque-forming cells (p.f.c.) in spleen and lung cells were found, though they were generally not statistically significant. The results suggest that the immune capacity in the lung and spleen can be influenced by exposure to CO.