A murine model for Streptococcus suis infection in pigs was validated by inoculating groups of 5 BALB/c and 5 CF1 mice with 107 CFU/ml of 13 different S. suis serotype 2 strains. The pathogenicity of these strains had been established in a standardized pig model of S. suis infection using one- week-old gnotobiotic pigs. We inoculated groups of mice intraperitoneally with 4 strains that were highly virulent for pigs and belonged to the phenotype MRP+EF+, with 4 strains, that were weakly virulent for pigs and belonged to the phenotype MRP+EF*, and with 5 strains that were non- virulent for pigs and belonged to phenotype MRP - EF -. The S. suis strains that were highly virulent for pigs caused high morbidity and an intermediate mortality in mice, the S. suis strains that were weakly virulent for pigs caused high morbidity but low mortality, and the strains that were non- virulent for pigs, induced highest morbidity and mortality. These results were comparable in both breeds of mice. In contrast to the pathology of S. suis infection in pigs with specific lesions, lesions in mice were histologically often characterized as non-specific, i.e., necrotizing encephalitis and focal or diffuse hepatitis sometimes with abscesses. Irrespective of breed (BALB/c vs. CF1), the murine model used for S. suis infection was incompatible with the pig model. This indicates that virulence of S. suis type 2 for mice and pigs is host-specific. Therefore, we regard the presently available murine models unsuitable for studying S. suis infections in pigs.