Missouri patients who fulfill the strict CDC surveillance definition for Lyme disease have been reported in significant numbers since 1987, although there are no viable Missouri human cultures of Borrelia burgdorferi. The Missouri erythema migrans rashes are indistinguishable from those in other areas, and the clinical syndrome appears similar to Lyme disease nationally. The authors suspect atypical B. burgdorferi, and/or other Borrelia spirochetes of causing this clinical borreliosis syndrome.