Both humans and rats with liver cirrhosis have increased morbidity and mortality from pneumococcal pneumonia. By use of a rat model of carbon tetrachloride-induced liver cirrhosis, uptake of fluorochrome-labeled Streptococcus pneumoniae by polymorphonuclear leukocytes (PMNL) and alveolar macrophages (AM) was examined by flow cytometry. Peripheral blood PMNL from cirrhotic rats showed no defect in phagocytic or bactericidal capacity for type 10A S. pneumoniae in vitro. However, in vivo, fewer type 3 S. pneumoniae were engulfed by PMNL in the lungs of cirrhotic rats with a concomitant increase in the number of organisms taken up by their AM in comparison with controls. These studies indicate the importance of using more relevant in vivo methodologies for assessing bacterial phagocytosis. In addition, the reduction in uptake of type 3 pneumococci by PMNL within the microenvironment of the cirrhotic rat lung could help to explain the increased susceptibility of cirrhotic rats to pneumococcal pneumonia.