Reovirus replicates with slower kinetics in the absence of Bid, and virus-induced apoptosis and CNS injury are diminished in Biddeficient animals. Although Bid contributes significantly to reovirus pathogenesis, our data do not allow us to determine whether diminished reovirus virulence in Bid-deficient animals is attributable to reduced capacity of reovirus to replicate in the CNS, diminished capacity of reovirus to injure neurons by apoptosis, or both effects. It is also not clear whether the decreased capacity of reovirus to evoke apoptosis in the CNS is a cause or effect of the lower viral titers at that site.