Cats vaccinated intranasally (i.n.) with a temperature sensitive feline infectious peritonitis virus (ts-FIPV) vaccine were protected against an FIP-inducing challenge. Seventeen of 20 vaccinated cats (85%) survived a rigorous virulent FIPV challenge that caused FIP in 12 of 12 non-vaccinated cats (100%), 10 (83%) of which died. Intranasal vaccination stimulated serum IgG and serum and salivary IgA antibody responses (measured by ELISA), FIPV-neutralizing antibody (VN), and a cell-mediated immune (CMI) response as measured by lymphocyte proliferation. The serum antibody response to vaccination was not associated with protection. In fact, the IgG, IgA and VN titres were much higher in control cats than in vaccinated cats following challenge suggesting an immune-mediated pathogenesis. In contrast, stimulation of a mucosal IgA response to vaccination was related to protection. The in vitro proliferation of peripheral blood lymphocytes in response to virulent FIPV was observed in vaccinated cats, in vaccinated and challenged cats but not in non-vaccinated challenged cats.