ABSTRACT. Pneumotropic virus invasion of parenchymal organs in mice with immunosuppressants is worth studying from an etiopathogenetic viewpoint as an animal model of a compromised host. This study analyzed the invasion by Sendai virus (SeV) of mouse organs in immunosuppressive states induced by cortisone (CO) and cyclophosphamide (CY). After subcutaneous inoculation of CO or CY, or both, in mice infected intra-nasally with SeV, the SeV invasion was investigated by detecting viremia and viral antigen in organs. SeV Nagoya strain and one treatment of CO or CY caused viremia at 18 hr or 3 d, respectively, with infection in tracheal lymph nodes, but not in untreated mice. SeV invaded hepatocytes and splenolymphocytes on days10 and 5-10, respectively, after infection. CO or CY treatment, three times, induced viral invasion of brain tissues or serious respiratory infection, respectively, but progressive invasion of abdominal parenchymal organs was not different between treated groups. One CO and two CY treatments intensified viral invasion into many organs, maintaining seronegativity. Cerebral blood vessels had the highest incidence of viral antigen in the brain. Astroglial sheets, choroid plexuses, pia maters, and ventricular epithelia tested positive; test-positive neurons were few. SeV MN strain caused progressive invasion of the brain with gliosis and neuronophagy. Blood-brain barrier disruption was caused by virulence of the MN strain. Half the infected mice in two groups treated with CO once and CY twice succumbed to delayed hypersensitivity, suggested by cerebromicrovascular nodulation. KEY WORDS: blood-brain barrier disruption, cortisone, cyclophosphamide, Sendai virus, viremia.