Tick-borne diseases are common in Oklahoma, especially the eastern part of the state where tick prevalence is highest. Three species of hard ticks are present in Oklahoma that are known vectors of human disease--the American dog tick (Rocky Mountain spotted fever; RMSF), the lone star tick (ehrlichiosis) and the black-legged tick (Lyme disease). Oklahoma consistently ranks among the top states in numbers of reported RMSF cases, and Ehrlichiosis may be as prevalent as RMSF. Although Lyme disease is frequently reported in Oklahoma, over-diagnosing of this disease due to false-positive test results is common; positive or equivocal screening tests should be confirmed by Western immunoblot. At present, it is unclear whether the disease seen here is Lyme disease or another Lyme-like disease. If true Lyme disease is present in the state, it is probably rare. Physicians should be aware of the most recent recommendations for diagnosis, therapy and prevention of tick-borne diseases.