Rat virus (RV) is a common parvovirus of laboratory rodents which can disrupt rat-based research. Prenatal or perinatal infection can be pathogenic or lead to persistent infection, whereas infection of adult rats is typically self-limiting. Effects on the host immune system have been documented during RV infection, but little is known about immune responses necessary for viral clearance. Our studies were conducted to identify humoral and cellular responses to the predominant capsid protein, VP2, during experimental infection of adult rats. We observed VP2-specific proliferation, gamma interferon production, and an immunoglobulin G2a humoral response that is maintained for at least 35 days following RV infection. These results strongly suggest the induction of virus-specific Th1-mediated immunity.