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 la-trans) 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%).