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To obtain data about select zoonotic and other infectious diseases in free-ranging predators in five ecoregions in Nebraska, sera were collected from 67 coyotes (Canis latrans) and 63 raccoons (Procyon lotor)) from November 2002 through January 2003. For coyotes, antibodies were detected against canine distemper virus (CDV, 61%), Francisella tularensis) (32%), Rickettsia rickettsi) (13%), and flaviviruses (48%). None of the coyote sera had antibodies to Borrelia burgdorferi, Brucella canis), or six serovars of Leptospira interrogans). Because serologic cross-reactivity exists among flaviviruses, 14 sera from flavivirus-positive coyotes were also tested for St. Louis encephalitis virus (SLE) antibodies and two (14%) were positive, suggesting that up to 48% of coyotes tested had antibodies against West Nile virus (WNV). For raccoons, antibodies were detected against CDV (33%), F. tularensis) (38%), and three serovars of L. interrogans) (11%).