Reovirus virulence correlates with its capacity to cause apoptosis [4, 7, 11, 12, 48, 49] . Given the central role of Bid in apoptosis induction by reovirus in cell culture, we hypothesized that reovirus apoptosis and virulence would be diminished in the absence of Bid. To test this hypothesis, we inoculated two-day-old wild-type and Bid-deficient mice perorally with a highly virulent, enteric, neurotropic reovirus strain, T3SA+ [50] , and monitored infected animals for signs of neurological disease and infection-induced morbidity over a period of 21 days ( Figure 5A ). Following inoculation with 10 4 PFU of T3SA+, most wild-type mice developed paralysis and respiratory distress. In contrast, the majority of Bid-deficient mice were asymptomatic. Consistent with this observation, ,91% of wild-type mice succumbed to reovirus infection with a median survival time of 11 days, whereas only ,30% of Bid-deficient mice died. Due to the relative resistance of Bid-deficient mice to reovirus-induced encephalitis, a median survival time could not be determined. Thus, the cellular apoptotic regulator Bid modulates reovirus-induced encephalitis.