Aim.To determine the incidence of overdiagnosis and overtreatment of Lyme disease in children residing in endemic areas using standardized CDC diagnostic criteria.Methods.Case series, using data collected prospectively from patients referred for Lyme disease to a tertiary care center located in an area endemic for Lyme disease. Data were collected on all referred cases during a 30-month period from August, 1995, to February, 1998.Results.We evaluated 216 patients with ages from birth to 18 years. Results of Lyme enzyme-linked immunosorbent assay and Western blot studies were available for all patients evaluated. Of these, 68 (31%) fulfilled the criteria for active Lyme disease, most commonly having arthritis, facial nerve palsy, aseptic meningitis or erythema migrans; 39 (18%) had a prior history of Lyme disease and were referred with an acute intercurrent illness or lower school grades attributed to the previous Lyme disease; 77% of these were receiving therapy at the time of referral; 109 (50%) of 216 had no past or current evidence of Lyme disease, yet 79% were receiving therapy at the time of referral.Conclusions.Overdiagnosis and overtreatment of Lyme disease is a major concern in areas endemic for Lyme disease, even after 1995 when standard criteria for diagnosis were published. The most common problem in diagnosis was misinterpretation of Western immunoblot results.