Tularemia is a zoonotic disease caused by Francisella tularensis, a fastidious, gram-negative coccobacillus that infects vertebrates, especially rabbits and rodents. In humans, tularemia is classified into six major syndromes: ulceroglandular (the most common form), glandular, typhoidal, oculoglandular, oropharyngeal, and pneumonic. The case-fatality rate among humans can reach 30%-60% in untreated typhoidal cases. Although bites from ticks and handling infected animals are considered the most common modes of tularemia transmission in the United States, the disease also is spread through ingestion of contaminated food or water, inhalation, and insect bites. During 2001-2003, Wyoming experienced an increase in reported human cases of tularemia. This report describes the subsequent investigation by the Wyoming Department of Health (WDH), which indicated that 1) insect bites (particularly from deerflies and other horseflies) were the most commonly reported likely mode of transmission, and 2) the increase in cases was geographically and temporally associated with an outbreak of tularemia among rabbits in southwestern Wyoming. To obtain a timely diagnosis and provide information on appropriate preventive measures, health-care providers and public health officials should have knowledge of the local epidemiology of tularemia, particularly regarding modes of transmission and resultant clinical syndromes.