Each year, many residents of and visitors to endemic regions of the western United States are exposed to the vector of tick-borne relapsing fever (TBRF), an underrecognized and underreported disease. Through review of report forms and literature review, we identified 450 cases of TBRF acquired in the United States in 11 western states (and in British Columbia by a U.S. resident) from January 1977 to January 2000. Exposure sites were in forested areas, at varying elevations, in mountainous regions (Cascade, Rocky Mountain, San Bernardino, and Sierra Nevada ranges) of the United States and Canada and in limestone caves in central Texas. Only 13 counties accounted for approximately 50% of all cases. Forty percent of the cases were not residents of the state where TBRF exposure occurred, including 7% from 11 states where TBRF is not endemic. TBRF is endemic in the United States and is a disease affecting travelers, who may return home with the disease to areas where physicians are not familiar with it.