We describe two cases of West Nile (WN) encephalitis in a married couple in Tel Aviv, Israel, in 1999. Reverse transcription-polymerase chain reaction performed on a brain specimen from the husband detected a WN viral strain nearly identical to avian strains recovered in Israel in 1998 (99.9% genomic sequence homology) and in New York in 1999 (99.8%). This result supports the hypothesis that the 1999 WN virus epidemic in the United States originated from the introduction of a strain that had been circulating in Israel.