To distinguish between the contributions of neutrophils and cell-mediated immunity to defense against Nocardia asteroides in the lung, we induced pneumonia in BALB/c mice by intranasal inoculation. We studied the course of pneumonia by histology, bronchoalveolar lavage, and quantification of colony-forming units in lungs. Mice with intact host defenses had an initial inflammatory response, consisting mostly of neutrophils, followed by a mononuclear cell infiltrate. Nocardiae were eradicated during the seven days after inoculation. Mice in which the early, predominantly neutrophil inflammatory response was prevented with mechlorethamine or antiserum to neutrophils had little inflammation, and nocardiae grew extensively. Mice in which cell-mediated immunity was impaired with cyclosporin A or cortisone acetate developed abscesses; neutrophils were abundant, but nocardiae proliferated. The occurrence of these three separate and distinct patterns suggested that both neutrophils and cell-mediated immunity are necessary for optimal control of N. asteroides infection.