Twenty seven patients presenting with mono/oligoarticular disease of unknown etiology were prospectively screened for Lyme arthritis. In addition, 12 healthy blood bank donors, 25 individuals with rheumatoid arthritis (disease controls), and 20 deer handlers and veterinarians were also screened for IgG antibodies to Borrelia burgdorferi. Only one patient tested borderline positive for antibodies to B. burgdorferi (more likely false positive). None of the healthy subjects, disease controls or occupationally exposed individuals exhibited serological evidence of exposure to B. burgdorferi. Screening for Lyme disease may not be warranted while investigating mono/oligoarthritides of unknown etiology in this part of the country.