Tickborne relapsing fever (TBRF) is a bacterial illness caused by certain species of Borrelia and transmitted through brief and painless bites from Ornithodoros ticks. Illness usually is characterized by intermittent periods of fever, fatigue, and muscle aches. In April 2005, CDC received reports of two cases of severe TBRF associated with acute respiratory distress syndrome (ARDS) in residents of California and Nevada. After a report describing these cases was posted on CDC's Epidemic Information Exchange (Epi-X), health officials in Washington reported a third severe case associated with ARDS. This report summarizes these three cases and the results of the subsequent epidemiologic investigations. The findings indicate that ARDS might occur more frequently in patients with TBRF than previously recognized. Optimal management of TBRF requires both prompt diagnosis and careful observation during the initial phases of treatment.