Secondary specific pathogen-free (sSPF) piglets were inoculated intranasally with Streptococcus suis serotype 2 alone, porcine reproductive and respiratory syndrome virus (PRRSV) alone, or with PRRSV followed by S suis. Uninfected piglets were used as controls. Pigs inoculated with PRRSV (ATCC VR-2332) followed by challenge with a virulent strain (87555) of S suis serotype 2 developed clinical signs, suppurative meningitis and large numbers of S suis in their tissues, including the brain and meninges. Pigs inoculated with PRRSV alone, S suis (87555) alone, or with PRRSV and the DH5 strain of S suis serotype 2 (lacking a protein associated with virulence) and the uninfected piglets did not develop clinical signs or lesions or have large numbers of bacteria in their tissues. The results suggest that PRRSV predisposes sSPF pigs to infection and disease caused by virulent S suis serotype 2. Co-infection of piglets with PRRSV and a virulent strain of S suis may provide a useful model for the study of S suis septicaemia and meningitis.