We inoculated 5 to 7-week-old female C3HeB/FeJ mice with Streptococcus pyogenes strain B514-Sm (type M50) by both an intranasal and intratracheal route and characterized the resulting illness. Following intranasal inoculation, the animals developed signs of illness within 1 to 8 days post-inoculation which correlated with acute, suppurative, bronchopneumonia during histopathologic analysis; however, the relationship of response to dose was non-linear, as seen previously in a small group of mice. Intratracheal inoculations were then performed to increase the quantitative reliability of the model. Following intratracheal inoculation, the animals succumbed to an illness that was indistinguishable from that seen after intranasal inoculation, and the incidence of pneumonia followed a steep dose response curve. The dose at which 50% of the animals exhibited signs of respiratory illness within 72 h was 1.0 x 10(7) colony forming units. All of the animals that appeared ill had lung lesions as determined by gross and histopathologic examination. Bacteraemia followed pneumonia in two-thirds of the intratracheally inoculated animals, indicating that the S. pyogenes had crossed tissue barriers. We hope that this model will be useful in future studies concerning the role of suspected streptococcal virulence factors in the later stages of pathogenesis of invasive S. pyogenes infection.