Canine parvovirus (CPV) type-2 emerged as a new virus infecting dogs in 1978, and it was probably derived as a variant of feline panleukopenia virus or of a closely related virus infecting another carnivore. CPV type-2 was subsequently replaced in nature by antigenically variant viruses (CPV type-2a and CPV type-2b) which now coexist in dog populations worldwide. We show that CPV type-2 isolates did not replicate in cats, but that both CPV type-2a and CPV type-2b isolates replicated efficiently. About 10% of the viruses isolated from cats with natural parvovirus disease were antigenically indistinguishable from CPV type-2a or type-2b. The capsid protein gene sequence of a 1990 feline parvovirus isolate ("FPV-24") was essentially identical to the sequence of CPV type-2b viruses from dogs. The loss and reacquisition of the feline host range in CPV was most likely due in each case to small numbers of changes in a region of the virus capsid where three protein monomers interact.