The effects of inhalational anesthetics on brain penetration by the neurovirulent noninvasive West Nile virus (WN-25) were studied in mice. WN-25 injected intracerebrally causes encephalitis and kills adult mice, but when injected intraperitoneally (i.p.) it is unable to invade the brain and kill. Under stress conditions, this strain causes encephalitis and death even after i.p. inoculation. In the study described in this paper, we used two inhalational anesthetics, a single short-term exposure to 2% halothane for 10 min in oxygen, or 70% nitrous oxide (N2O) for 30 min in air. Both inhalational anesthetics induced WN-25 encephalitis and death in 33% and 20% of the tested mice, respectively. Exposure of inoculated mice to halothane for prolonged periods or for repeated exposures (two or three times) markedly increased the mortality rate (up to 75%). Exposure to 30% CO2, a known modulator of blood-brain barrier (BBB) activity, was used as a positive control (80% mortality). No death was observed in the control non-exposed injected mice. Virus levels were found to be more than 10(7) plaque-forming units (PFU)/brain in all moribund mice. Additional parameter demonstrating the "stressor-like" nature of inhalation anesthetics was the induction of a significant decrease in weight of the lymphoid organs of inoculated mice. We suggest that inhalational anesthetics induces BBB breaching with subsequent entrance of the noninvasive WN-25 virus into the brain, causing encephalitis and death.