Examination of strain differences in the susceptibility of mice to experimental respiratory tract infection with penicillin-resistant Streptococcus pneumoniae TUM19 revealed that a fatal infection model could be induced in immunocompetent CBA/J mice, but not in C3H/HeN, C57BL/6 or ICR mice. After intranasal instillation of c. 10(6) cfu of S. pneumoniae, the bacterial counts in the lungs of CBA/J mice increased from 10(5) to 10(7) cfu after 3-5 days, and gradually increased thereafter. The challenge organisms localised mainly in the lungs until 14 days after infection. Mice began to die c. 7 days after infection, and by 3 weeks most of the mice had died. Histopathologically, infiltration of neutrophils and lymphocytes around bronchi was observed from 1 day after infection, and fibrin deposition was seen in alveolar and bronchial spaces from 5 days. This model may be useful for investigating therapy of respiratory tract infection caused by penicillin-resistant S. pneumoniae because its pathological features resemble those observed in the human disease.